Abstract: Objective To investigate the relationship between perineural invasion (PNI) and lymph node metastasis (LNM) in patients with gastric cancer, and to evaluate the prognostic significance of PNI in patients undergoing radical gastrectomy.Methods Retrospective analysis was conducted on 225 patients with stage Ⅰ-Ⅲ gastric cancer who were admitted to the Affiliated Hospital of Xuzhou Medical University from September 2018 to July 2021. Differences in clinicopathological characteristics between patients with different PNI statuses were compared. Univariate and multivariate logistic regression analyses were performed to identify factors associated with LNM. Kaplan-Meier survival curves were constructed, and univariate and multivariate Cox regression analyses were used to evaluate factors affecting overall survival.Results Significant differences were observed between PNI-positive and PNI-negative patients in terms of CA199 level, CA242 level, depth of tumor invasion, number of lymph node metastases, degree of differentiation, TNM stage, and vascular invasion (all P<0.05). Multivariate logistic regression analysis showed that tumor invasion depth and vascular invasion were independent risk factors for LNM. Kaplan-Meier analysis demonstrated that overall survival was significantly shorter in PNI-positive patients than in PNI-negative patients (P<0.001). Multivariate Cox regression analysis indicated that PNI (HR=1.903, 95%CI: 1.144-3.166, P=0.013) was an independent prognostic factor for overall survival in gastric cancer patients.Conclusions PNI is closely associated with multiple clinicopathological characteristics in gastric cancer, but is not an independent risk factor for LNM. Tumor invasion depth and vascular invasion are independent risk factors for LNM. PNI is an independent prognostic factor for overall survival in patients undergoing radical gastrectomy and may help improve prognostic evaluation.