To investigate the expression and significance of G3BP and RhoC proteins in esophageal squamous carcinoma (ESC).The expression of G3BP and Rhoc proteins in 80 cases of ESC was detected by immunohistochemistry. The relationship was studied between the expression of the two proteins and tumor size, differentiation degree, TNM stage, lymph node metastasis and prognosis of ESC.The positive expression rate of G3BP in ESC was 71.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (Z = -2.283, P = 0.022), but no relations were found between G3BP expression and tumor size, differentiation degree and TNM stage (P > 0.05). The group with G3BP positive expression had shorter survival time than the group with G3BP negative expression (P = 0.000). The positive expression rate of RhoC in ESC was 66.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (Z = -2.115, P 0.05). The RhoC positive expression group had a shorter survival time than the RhoC negative expression group (P < 0.001. The expression of G3BP protein correlated positively with the expression of RhoC in ESC tissues (rs = 0.656, P < 0.001).The expression of G3BP and RhoC protein is closely related to the lymph node metastasis and survival in ESC patients. G3BP and RhoC proteins can be considered as predictors of prognosis in ESC patients.