Abstract: Objective To explore the expressions of stomatin like protein 2（STOML2） and tripartite motifcontaining 25（TRIM25） in the hepatocellular carcinoma（HCC） tissues as well as their relationship with clinicopathological characteristics. Methods The expressions of STOML2 and TRIM25 in 75 cases of HCC and 61 adjacent normal liver tissues were detected by immunohistochemical EnVision two-step method. The results were graded according to the intracellular staining intensity and the number of positive cells. Then the relationship of STOML2， TRIM25 expressions and the clinicopathological characteristics of HCC and the correlation of two proteins were analyzed. Meanwhile， the KaplanMeier survival curve was used to analyze the overall survival（OS） of HCC patients with different intensity of TRIM25 and STOML2. Results The over-expression rates of STOML2 and TRIM25 in HCC tissues were 68.0％（51/75） and 64.0％（48/75）， both higher than 24.6％（15/61） and 37.7％（23/61） of the para-cancer tissues（P＜0.01）. The expression of STOML2 was related to tumor size， differentiation degree， BCLC staging， portal tumor thrombus and extrahepatic metastasis， while the expression of TRIM25 was associated with the AFP before treatment， differentiation degree and ascites（P＜0.05）. STOML2 was positively correlated with TRIM25（r=0.379，P=0.001）. The median OS of patients with highlevel TRIM25 was 21.0 months， lower than 36.5 months of patients with low-level TRIM25（P＜0.05）， but there was no significant difference of median OS between patients with different levels of STOML2（P＞0.05）. Conclusion STOML2 and TRIM25 are highly expressed in HCC tissues and the combined detection of STOML2 and TRIM25 should probably be helpful for the evaluation the malignancy and differentiation of HCC. TRIM25 may be useful for the assessment and prediction of prognosis of HCC.