This study investigates the molecular mechanisms of pancreatic cancer liver metastasis, focusing on the role of PAK2. The research team used single-cell sequencing data and bulk data to identify genes associated with liver metastasis. They employed various bioinformatics methods, including high-dimensional weighted gene co-expression network analysis (hdWGCNA), machine learning algorithms, and COX regression models, to screen genes related to patient prognosis. The study identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis showed that PAK2 activates the TGF-β signaling pathway, promoting liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis showed that PAK2 overexpression promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. Functional experiments showed that silencing PAK2 reduced the proliferative capacity and invasion capability of pancreatic cancer cells. The study concludes that PAK2 facilitates the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-β signaling pathway. PAK2 also decreases the differentiation level of cancer cells, enhancing their malignancy. Additionally, PAK2 fosters communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. PAK2 is a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis. The study highlights the importance of understanding the molecular mechanisms of pancreatic cancer liver metastasis for the development of effective treatment strategies.This study investigates the molecular mechanisms of pancreatic cancer liver metastasis, focusing on the role of PAK2. The research team used single-cell sequencing data and bulk data to identify genes associated with liver metastasis. They employed various bioinformatics methods, including high-dimensional weighted gene co-expression network analysis (hdWGCNA), machine learning algorithms, and COX regression models, to screen genes related to patient prognosis. The study identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis showed that PAK2 activates the TGF-β signaling pathway, promoting liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis showed that PAK2 overexpression promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. Functional experiments showed that silencing PAK2 reduced the proliferative capacity and invasion capability of pancreatic cancer cells. The study concludes that PAK2 facilitates the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-β signaling pathway. PAK2 also decreases the differentiation level of cancer cells, enhancing their malignancy. Additionally, PAK2 fosters communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. PAK2 is a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis. The study highlights the importance of understanding the molecular mechanisms of pancreatic cancer liver metastasis for the development of effective treatment strategies.