This review summarizes the current state of research on histone deacetylase (HDAC) inhibitors (HDACis) in the treatment of solid tumors. HDACs are critical regulators in the pathogenesis of various malignancies, and HDACis have been developed to target these enzymes. Preclinical studies have shown that HDACis can effectively inhibit tumor growth, either as monotherapy or in combination with other treatments. Clinical trials have evaluated the potential of selective and pan-HDACis in treating solid tumors, but some trials have failed to achieve expected therapeutic outcomes. Factors such as experimental design, toxicological side effects, tumor heterogeneity, and off-target effects have contributed to these failures. Despite these challenges, advancements in HDACi research and combination therapies are expected to improve the treatment of solid tumors. HDACs are classified into four classes (I, II, III, and IV) based on their homology to yeast proteins. Class I HDACs are nuclear proteins involved in transcriptional repression, chromatin assembly, and cell cycle progression. Class II HDACs are found in both the nucleus and cytosol and are involved in inflammation and migration. Class III HDACs are NAD+-dependent and play roles in metabolism and cell cycle regulation. HDACs regulate histone acetylation, which is crucial for gene expression and tumor progression. Elevated HDAC activity is associated with tumor growth, and HDACis can reverse this by increasing histone acetylation, leading to chromatin remodeling and tumor cell apoptosis. HDACis have shown promise in various cancers, including hematological malignancies, but their efficacy in solid tumors is limited. Combination therapies with other drugs, such as chemotherapy, targeted therapy, immunotherapy, and radiotherapy, have been explored to enhance the effectiveness of HDACis. Clinical trials have demonstrated that HDACis can sensitize cancer cells to these treatments by modulating chromatin structure, enhancing DNA damage, and improving immune responses. However, the clinical application of HDACis is still limited by issues such as toxicity, tumor heterogeneity, and the need for more selective inhibitors. Several HDACis, including Tucidinostat, Entinostat, and Vorinostat, have been evaluated in clinical trials for solid tumors. These trials have shown promising results in certain cancers, such as breast cancer and colorectal cancer, but have also highlighted the need for further research to optimize their use. The development of more selective HDACis and combination therapies is expected to improve the treatment of solid tumors. Despite challenges, HDACis remain a promising area of research with potential for future clinical applications.This review summarizes the current state of research on histone deacetylase (HDAC) inhibitors (HDACis) in the treatment of solid tumors. HDACs are critical regulators in the pathogenesis of various malignancies, and HDACis have been developed to target these enzymes. Preclinical studies have shown that HDACis can effectively inhibit tumor growth, either as monotherapy or in combination with other treatments. Clinical trials have evaluated the potential of selective and pan-HDACis in treating solid tumors, but some trials have failed to achieve expected therapeutic outcomes. Factors such as experimental design, toxicological side effects, tumor heterogeneity, and off-target effects have contributed to these failures. Despite these challenges, advancements in HDACi research and combination therapies are expected to improve the treatment of solid tumors. HDACs are classified into four classes (I, II, III, and IV) based on their homology to yeast proteins. Class I HDACs are nuclear proteins involved in transcriptional repression, chromatin assembly, and cell cycle progression. Class II HDACs are found in both the nucleus and cytosol and are involved in inflammation and migration. Class III HDACs are NAD+-dependent and play roles in metabolism and cell cycle regulation. HDACs regulate histone acetylation, which is crucial for gene expression and tumor progression. Elevated HDAC activity is associated with tumor growth, and HDACis can reverse this by increasing histone acetylation, leading to chromatin remodeling and tumor cell apoptosis. HDACis have shown promise in various cancers, including hematological malignancies, but their efficacy in solid tumors is limited. Combination therapies with other drugs, such as chemotherapy, targeted therapy, immunotherapy, and radiotherapy, have been explored to enhance the effectiveness of HDACis. Clinical trials have demonstrated that HDACis can sensitize cancer cells to these treatments by modulating chromatin structure, enhancing DNA damage, and improving immune responses. However, the clinical application of HDACis is still limited by issues such as toxicity, tumor heterogeneity, and the need for more selective inhibitors. Several HDACis, including Tucidinostat, Entinostat, and Vorinostat, have been evaluated in clinical trials for solid tumors. These trials have shown promising results in certain cancers, such as breast cancer and colorectal cancer, but have also highlighted the need for further research to optimize their use. The development of more selective HDACis and combination therapies is expected to improve the treatment of solid tumors. Despite challenges, HDACis remain a promising area of research with potential for future clinical applications.