The article reviews the pharmacological therapy for metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma (MSLD-HCC). MSLD, now known as metabolic dysfunction-associated fatty liver disease (MAFLD), is emerging as a leading cause of HCC due to its increasing prevalence, particularly in patients with type 2 diabetes and obesity. The review highlights the distinctive features of MSLD-HCC, including patient demographics, clinicopathological characteristics, and the distinct progression from MSLD to HCC. It discusses the underlying mechanisms of MSLD-HCC, such as chronic inflammation, oxidative stress, gut dysbiosis, and metabolic imbalances. The article also reviews the latest advancements in pharmacological therapies, including anti-inflammatory drugs, antioxidant drugs, anti-fibrosis drugs, drugs regulating lipid metabolism, and gut microbiota regulators. These treatments aim to inhibit the progression of MSLD to HCC by targeting various mechanisms, such as reducing inflammation, oxidative stress, fibrosis, and lipid accumulation. The review emphasizes the need for further research to understand the exact molecular mechanisms and to develop effective treatments for MSLD-HCC.The article reviews the pharmacological therapy for metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma (MSLD-HCC). MSLD, now known as metabolic dysfunction-associated fatty liver disease (MAFLD), is emerging as a leading cause of HCC due to its increasing prevalence, particularly in patients with type 2 diabetes and obesity. The review highlights the distinctive features of MSLD-HCC, including patient demographics, clinicopathological characteristics, and the distinct progression from MSLD to HCC. It discusses the underlying mechanisms of MSLD-HCC, such as chronic inflammation, oxidative stress, gut dysbiosis, and metabolic imbalances. The article also reviews the latest advancements in pharmacological therapies, including anti-inflammatory drugs, antioxidant drugs, anti-fibrosis drugs, drugs regulating lipid metabolism, and gut microbiota regulators. These treatments aim to inhibit the progression of MSLD to HCC by targeting various mechanisms, such as reducing inflammation, oxidative stress, fibrosis, and lipid accumulation. The review emphasizes the need for further research to understand the exact molecular mechanisms and to develop effective treatments for MSLD-HCC.