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AIM: To investigate the expression of p57kip2 and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma (HCC). METHODS: Expression of p57kip2, PCNA and p53 in tumor tissues from 32 patients with HCC and 10 liver tissues of normal persons was detected with Elivision immunohistochemical technique. RESULTS: The p57kip2 protein positive-expression rate in HCC was 56.25%, lower than that in normal tissues (100%, P<0.05). The reduced expression of p57kip2 protein correlated significantly with moderate or low differentiation of tumor cells (P = 0.007 <0.05), high clinical stage (P= 0.041 <0.05) and poor prognosis (P= 0.036 <0.05), but did not correlate significantly with metastasis, tumor size, level of AFP and age (P>0.05). The PCNA positive-expression rate was 56.25%, which was correlated significantly with the expression of p57kip2 (P= 0.025<0.05). The p53 positive-expression rate was 46.88%, which was not correlated significantly with the expression of p57kip2 (P>0.05). CONCLUSION: There is a marked loss or absence of p57kip2 expression and high expression of PCNA in HCC, which are involved in carcinogenesis and development of HCC. The p57kip2 and p53 may induce apoptosis via different mechanisms.