Liver metastasis is a common event at the advanced stage of pancreatic malignancies. Identification of effective therapeutic targets is crucial for the management of pancreatic cancer patients with liver metastases. In this study, we show that (A) AUTS2 is overexpressed in liver metastases of pancreatic cancer and could be a biomarker for defining cancer subtypes. (B) AUTS2 expression is positively correlated with Docetaxel resistance, TGF-beta pathway activation, HEDGEHOG and WNT signaling pathway. (C) By building an AUTS2 centered protein-drug interaction network, we show that AUTS2 might promote chemotherapeutic resistance and metastasis by exerting its effect on epithelial-mesenchymal transition and WNT signaling pathway. (D) Five drugs that could down regulate the expression of AUTS2 were also suggested. These drugs might help in the treatment of pancreatic cancer patients at the stage of liver metastasis. In summary, our results indicate that AUTS2 is a candidate biomarker for defining liver metastasis of pancreatic cancer and directing personalized therapies.