Abstract: Objective To investigate the expression of c-Jun activation domain binding protein 1 (JAB1) and its relationship with expressions of P27 protein in human hepatocellular carcinoma (HCC), and to determine whether JAB1 is associated with clinicopathological parameters and prognosis of HCC. Methods Immunohistochemical analysis was performed to investigate the expression of JAB1 and P27 in 76 cases of HCC and adjacent nontumorous tissues. Fresh tumor tissues and their adjacent nontumorous tissues from 8 cases of HCC were collected for Western blot and immunoprecipitation assays. Results The expression of JAB1 in HCC was significantly higher than that in adjacent nontumorous tissues. In contrast, P27 levels were higher in nontumorous liver tissues than in HCC. JAB1 overexpression was correlated with histological differentiation, serum alpha-fetal protein(AFP) levels and metastasis (P<0.05). In addition, a negative correlation between JAB1 and P27 expression was found in HCC (r=-0.7077, P<0.001) ,and co-immunoprecipitation experiments demonstrated a direct interaction between JAB1 and P27 in HCC. In both Kaplan-Meier Plot and multivariate Cox regression analysis, the overexpression of JAB1 was significantly associated with poor prognosis (P<0.05). Conclusions JAB1 expression is inversely correlated with P27 expression levels, and JAB1, as a negative regulator of P27, may be associated with the progression and prognosis of HCC.