Objective：To investigate the expressions of proteins associated with chemotherapy resistance including excision repair cross-complementation group 1（ERCC1） in gastric cancer patients perineural invasion（PNI）. Methods：A retrospective study was conducted in 242 patients with gastric adenocarcinoma. The expressions of tubulin β3，thymidylate synthase（TS），P-glycoprotein，topoisomerase 2-alpha（TOP2A） and ERCC1 were detected by immunohistochemistry in paraffin-embedded tumor tissues and were compared between patients with and without PNI. Results：PNI was detected in 108 patients（44.6%），and the proportions of patients with the longest diameter of tumor ≥5 cm，poor histological differentiation，lymphovascular invasion and TNM stages of Ⅲ~Ⅳ were significantly higher in these patients than those in patients without PNI（P < 0.05）. The high expression rate of ERCC1 in patients with PNI was significantly higher than those in those without PNI（63.9% vs. 46.5%，P < 0.05），and this difference was mainly found in subgroups of male（64.8% vs. 43.1%，P=0.026） and poor differentiation（76.3% vs. 42.9%，P=0.006）. The high expression rates of tubulin β3，TS，P-glycoprotein and TOP2A were not significantly different between these two groups（P > 0.05）. Conclusion：Gastric cancer patients with PNI had an increased expression level of ERCC1 protein，indicating the possible mechanism of poor chemotherapy effect induced by PNI.