This study investigates the molecular mechanisms underlying pancreatic cancer liver metastasis, focusing on the role of PAK2. Using single-cell sequencing data and bulk data from various databases, the researchers identified PAK2 as a key gene promoting liver metastasis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning algorithms were used to screen and validate genes associated with liver metastasis. PAK2 was found to activate the TGF-beta signaling pathway, promoting liver metastasis, and was correlated with a lower differentiation status of pancreatic cancer cells. Additionally, PAK2 enhanced communication between cancer cells and the tumor microenvironment, increased chemoresistance, and modulated metabolic pathways. Functional experiments in PANC-1 and Bx-PC-3 cells confirmed that silencing PAK2 reduced proliferation and invasion, and inhibited apoptosis. The study concludes that PAK2 is a pivotal gene in pancreatic cancer liver metastasis, and targeting its expression may offer a promising therapeutic strategy to prevent liver metastasis and improve prognosis.This study investigates the molecular mechanisms underlying pancreatic cancer liver metastasis, focusing on the role of PAK2. Using single-cell sequencing data and bulk data from various databases, the researchers identified PAK2 as a key gene promoting liver metastasis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning algorithms were used to screen and validate genes associated with liver metastasis. PAK2 was found to activate the TGF-beta signaling pathway, promoting liver metastasis, and was correlated with a lower differentiation status of pancreatic cancer cells. Additionally, PAK2 enhanced communication between cancer cells and the tumor microenvironment, increased chemoresistance, and modulated metabolic pathways. Functional experiments in PANC-1 and Bx-PC-3 cells confirmed that silencing PAK2 reduced proliferation and invasion, and inhibited apoptosis. The study concludes that PAK2 is a pivotal gene in pancreatic cancer liver metastasis, and targeting its expression may offer a promising therapeutic strategy to prevent liver metastasis and improve prognosis.