Objective:To explore the predictive value of T helper 22 cell(Th22) combined with circulating tumor cells(CTCs) for peritoneal metastasis of gastric cancer. Methods: A total of 120 patients with gastric cancer admitted to Huai'an Hospital of Huai'an City January 2022 to January 2025 were consecutively enrolled. According to the presence of peritoneal metastasis, the patients were divided into the metastasis group(38 cases) and the non-metastasis group(82 cases). The percentage of Th22 cells and the count of CTCs were detected and compared between the two groups. Logistic regression analysis was used to screen the risk factors for peritoneal metastasis of gastric cancer, and the receiver operating characteristic(ROC) curve was used to evaluate the predictive value of Th22 cells percentage combined with CTCs count for peritoneal metastasis of gastric cancer. Results: Among the gastric cancer patients, the proportion of poorly differentiated tumors, depth of invasion(T2), lymphatic vessel invasion, number of lymph node metastases, levels of carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA199), as well as the percentage of Th22 cells and the count of CTCs in the metastasis group were all significantly higher than those in the non-metastasis group(all P < 0.05). Logistic regression analysis showed that Th22 cells percentage and CTCs count were risk factors for peritoneal metastasis of gastric cancer. After adjusting for poorly differentiated tumors, depth of invasion(T2), lymphatic vessel invasion, number of lymph node metastases, CEA, and CA199, multivariate logistic regression analysis confirmed that Th22 cells percentage and CTCs count remained independent risk factors for peritoneal metastasis of gastric cancer(all P < 0.05). The correlation analysis showed that there was a significant positive correlation between Th22 cells percentage, CTCs count, and low differentiation of gastric cancer, depth of invasion T2, lymphatic vessel invasion, serum CEA, and CA199. Moreover, there was also a significant positive correlation between Th22 cells percentage and CTCs count(all P < 0.05). ROC curve analysis showed that the area under the curve(AUC) of Th22 cell percentage and CTCs count for predicting peritoneal metastasis of gastric cancer was 0.800 and 0.831, respectively. The AUC of the combined detection of the two indicators was 0.943, which was significantly larger than that of each indicator alone(Z=3.014, 2.937; all P < 0.05). Conclusion:Both Th22 cells percentage and CTCs count are independent risk factors for peritoneal metastasis of gastric cancer, and they are positively correlated with the malignant pathological features of gastric cancer and the levels of serum tumor markers. The combined application of the two shows good predictive value for peritoneal metastasis of gastric cancer.