Objective:To investigate the impact of human epidermal growth factor receptor 2 (HER2) and C-reactive protein/albumin ratio (CAR) on the long-term survival of gastric cancer patients after surgery.Methods:A retrospective analysis was conducted on 136 gastric cancer patients admitted to Lishui Central Hospital from January 2015 to December 2017, who underwent radical surgery and were followed up for 5 years. Patients were divided into HER2 positive and HER2 negative groups based on HER2 immunohistochemical results, and into high CAR and low CAR groups based on the CAR mean value. The relationship between HER2 and CAR with clinicopathological characteristics of gastric cancer patients was analyzed. The postoperative tumor-free survival rate and overall survival rate were compared between the two groups of patients (HER2 positive group and HER2 negative group, as well as high CAR group and low CAR group). Cox regression analysis was used to identify independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients.Results:The proportion of HER2 positive patients with large tumor size, low differentiation, T 3-4 tumor invasion depth, lymph node metastasis, and vascular invasion was significantly higher than that of HER2 negative patients (all P<0.05). The proportion of high CAR patients with large tumor size, low differentiation, T 3-4 tumor invasion depth, lymph node metastasis, and vascular invasion was significantly higher than that of low CAR patients (all P<0.05). Kaplan-Meier survival analysis showed that HER2 negative patients had significantly higher 1-year, 3-year, and 5-year cumulative tumor-free survival rate and overall survival rate than HER2 positive patients, while low CAR patients had significantly higher 1-year, 3-year, and 5-year cumulative tumor-free survival rate and overall survival rate than high CAR patients (all P<0.05). Multivariate Cox regression analysis identified T 3-4 tumor invasion depth, lymph node metastasis, HER2 positivity, and high CAR expression as independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients (all P<0.05). HER2 positive gastric cancer patients had a 1.895-fold higher risk of postoperative tumor recurrence and metastasis than HER2 negative patients ( HR: 1.895, 95% CI: 1.245-4.229, P=0.034), while high CAR gastric cancer patients had a 1.769-fold higher risk of postoperative tumor recurrence and metastasis than low CAR patients ( HR: 1.769, 95% CI: 1.433-3.959, P=0.039). HER2 positive gastric cancer patients had a 2.145-fold higher risk of postoperative death than HER2 negative patients ( HR: 2.145, 95% CI: 1.378-4.589, P=0.028), while high CAR gastric cancer patients had a 1.926-fold higher risk of postoperative death than low CAR patients ( HR: 1.926, 95% CI: 1.564-3.853, P=0.025). Conclusions:HER2 and CAR are independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients. Gastric cancer patients with HER2 positivity and high CAR have a higher risk of postoperative tumor recurrence, metastasis, and death. This study has some limitations due to its small sample size and single-center design, which may introduce some bias. Future multicenter and large-scale studies are needed to confirm the results of this study.