Objective To compare the positive rate of zinc finger protein A20, NF-κB p65 protein, and P-glyco- protein between primary hepatocellular carcinoma (HCC) tissues and paratumor tissues, and to explore the relationship between the 3 kinds of proteins and pathological features of HCC. Methods Thirty-two HCC tissues and 26 paratumor tissues resected from patients with HCC treated in our hospital from Feb. 2009 to Aug. 2010 were enrolled. Clinical data were also collected from files. The expressions of zinc finger protein A20, NF-κB p65 protein, and P-glycoprotein were tested by immunohistochemistry. Results The positive rate of zinc finger protein A20, NF-κB p65 protein, and P-glycoprotein in HCC tissues were 87.5%(28/32), 81.3%(26/32), and 65.6%(21/32), respectively, which were higher than that in paratumor tissues〔61.5%(16/26), 34.6%(9/26), and 30.8%(8/26), respectively〕, P<0.05. The three kinds of proteins were all closely related with HbsAg, and zinc finger protein A20 was related with cirrhosis in addition (P<0.05). Conclusions The positive rate of zinc protein A20, NF-κB p65 protein, and P-glycoprotein are much higher in primary HCC tissues than that in paratumor tissus, and they may play an important role in preoperative determination of hepatic tumors.