Abnormal AKR1C2 expression has been observed in many malignant human tumors, but its relationship with hepatocellular carcinoma(HCC) is not well understood so far. In order to evaluate hepatocarcinogenic effect of AKR1C2 gene and the significance of its abnormal expression in hepatocellular carcinoma, AKR1C2 gene is analysed by preparing rabbit anti-human AKR1C2 polyclonal antibody, constructing of AKR1C2 frameshift mutant and exploring RT-PCR, in situ hybridization, immunohistochemistry, Western blot, Northern blot, cDNA expression microarray, co-immunoprecipitation and the tumorigenicity assay in vivo and in vitro etc. AKR1C2 gene expression and its effects was analyzed, including 68 pairs of HCC specimens and its adjacent para-cancerous tissues, 8 cases of normal liver tissues and QGY7703 cell line. Results showed AKR1C2 expression was up-regulated among these patients, when compared with those of para-cancerous and normal liver tissues. Over- expression of AKR1C2 is also found to be correlated with high metastasis potentiality of HCC. AKR1C2 overexpression stimulates DNA synthesis, apoptosis, growth in soft agar and promote tumor formation and lead to expression differences of tumor genes. AKR1C2 mediated the NF-κB-dependent resistance of QGY7703 cells to anti-fas killing. Intracellar binding of AKR1C2 and Cdk4 was found. Abnormal expression of AKR1C2 gene may contribute to the occurrence, advancement and invasiveness of HCC from Qidong, China, a liver cancer high risk area.