Proteinase-activated receptor-2 (PAR2) is closely linked to tumor malignancy, but its biological role in cancer remains underexplored. In this study, we assessed PAR2 expression in lung adenocarcinoma (LUAD) and normal lung tissues, analyzed associations between clinicopathological features and survival rates, and confirmed that PAR2 promotes apoptosis resistance and reduces cisplatin-induced cytotoxicity in lung cancer cells. Using TCGA datasets, western blotting, qPCR, and immunohistochemistry (IHC), we observed a significant increase in PAR2 levels in LUAD samples compared to normal tissues (P<0.05), with high PAR2 expression correlating with poor differentiation and lymphatic invasion (P<0.05). Upregulated PAR2 was associated with reduced survival. Additionally, PAR2 inhibition increased the BAX/BCL-2 axis and contributed to cisplatin-induced endoplasmic reticulum stress and apoptosis in H1299 cells. However, PAR2 inhibition reduced cisplatin-induced ATF4 expression. Overall, PAR2 upregulation is strongly associated with poor postoperative survival, differentiation, and lymphatic metastasis in LUAD and modulates cisplatin cytotoxicity.