Abstract: Objective To investigate the expression of suppressor of cytokine signaling (SOCS) family members SOCS2 and SOCS5 in gastric cancer tissues and its associations with the clinicopathological characteristics and prognosis of patients with gastric cancer.Methods The protein expression of SOCS2 and SOCS5 in 204 gastric cancer tissues and the corresponding adjacent non-tumor tissues was detected by Immunohistochemistry (SP method). The associations between SOCS2 and SOCS5 expression and clinicopathological parameters were analyzed, and survival analysis was performed in followed-up patients.Results The positive expression rates of SOCS2 and SOCS5 were both higher in gastric cancer tissues than in adjacent tissues. SOCS2 expression was associated with vascular invasion and perineural invasion, but showed no correlation with sex, age, tumor size, TNM stage, degree of differentiation, or lymph node metastasis. SOCS2 expression was not associated with prognosis. SOCS5 expression was not correlated with any clinicopathological parameter; however, among patients with TNM stage Ⅲ—Ⅳ gastric cancer, overall survival was significantly lower in those with negative SOCS5 expression than in those with positive SOCS5 expression, and SOCS5 was a prognostic factor in advanced gastric cancer. In addition, the median survival time of patients with concomitant positive expression of both SOCS2 and SOCS5 was significantly longer than that of patients with concomitant negative expression.Conclusions SOCS2 and SOCS5 are highly expressed in gastric cancer tissues and may play important roles in the occurrence, progression, and prognosis of gastric cancer. Their combined expression may synergistically improve prognosis.