Pancreatic cancer is a lethal malignancy with an extremely poor prognosis. Although many genes and noncoding RNAs have been found to regulate its progression, more regulators are needed to be understood to resolve its high lethality. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) plays crucial roles in the progression of various tumors, but its role in pancreatic cancer progression has not been studied. In this study, we found that ERO1L was significantly upregulated in pancreatic cancer cells and patients; its overexpression significantly promoted pancreatic cancer migration, invasion, and growth, while its knockdown significantly inhibited pancreatic cancer migration, invasion, and growth. Mechanism analysis suggested that ERO1L promoted many tumor-associated signaling pathways, especially the Wnt/catenin pathway;it could activate the Wnt/catenin pathway and upregulate the targets of the Wnt/catenin pathway. We further analyzed the correlation between ERO1L expression and the prognosis of patients, suggesting that patients with high ERO1L expression had short survival time; it is an independent prognosis factor for patients' prognosis. Together, we found that ERO1L was an oncogene for pancreatic cancer.