Objective To detect the expressions of Rab3A interacting protein (Rab3IP) in esophageal cancer tissues and to explore their correlations with the clinicopathological features and prognosis of the patients. Methods The expressions of Rab3IP in 109 esophageal cancer tissues and paired adjacent tissues was detected using immunohistochemical staining and western blot, respectively. The correlations of different patterns of Rab3IP expressions with the clinicopathological features of the patients were analyzed. Kaplan- Meier survival analysis was used to analyze the over-all survival and recurrence-free survival of the patients in relation with Rab3IP expressions. Cox regression were applied to analyse its prognostic value. Results Rab3IP were highly expressed in 70.6% (77/109) in the esophageal cancer tissues compared to their paired adjacent tissues 52.3% (57/109), the difference was statistically significant (P < 0.05). The expression of TRab3IP were correlated with tumor size, invasion depth, lymph node metastasis, and TNM staging (P < 0.05). Univariate and multivariate analysis showed that the expression of Rab3ip was an independent prognostic factor for overall survival time of esophageal cancer patients after operation (P < 0.05), and the overall survival time of low expression group was higher than that of high expression group (P < 0.05). The expression of rab3ip protein was an independent prognostic factor for tumor-free survival time in patients with esophageal cancer (P < 0.05), and the tumor free survival time in the low expression group was higher than that in the high expression group (P < 0.05). Conclusion Rab3IP are high expression in esophageal cancer tissues and can serve as new prognostic biomarkers for esophageal cancer.