OVO-like protein 1 (OVOL1) has been implicated in the progression of various human cancers; however, the prognostic and immunological significance, as well as its biological role in pancreatic cancer, are unknown. In this study, by analyzing multiple patient cohorts, OVOL1 was found to be elevated in pancreatic cancer, which was associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). Two nomogram survival models for predicting 1-, 2-, and 3-year OS and DSS with excellent accuracy were constructed, respectively. Tumors with elevated OVOL1 expression showed decreased immune cell infiltration, including CD8 T cells, NK cells, and cytotoxic cells, and increased tumor mutation burden (TMB). Enrichment analysis revealed that OVOL1 was related to various biological terms and signaling pathways. Knockdown of OVOL1 reduced the proliferation of pancreatic cancer cells and inhibited the ERK/JNK/p38 MAPK signaling pathway. Furthermore, OVOL1 was revealed to be hypomethylated in pancreatic cancer, with low levels of OVOL1 methylation predicting poor outcomes. Our findings suggest that upregulation of OVOL1 has prognostic value and is associated with the unfavorable immune microenvironment in pancreatic cancer. OVOL1 is crucial for pancreatic cancer cell proliferation, which could be attributed to its effect on the ERK/JNK/p38 MAPK signaling pathway.