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AIM: To investigate the prognostic value of the expression of connexin (Cx) 26, 32 and 43 messenger RNA (mRNA) in hepatocellular carcinoma (HCC) tissues.METHODS: Using a reverse-transcriptase polymerase chain reaction (RT-PCR), Cx 26, Cx 32 and Cx 43 mRNAs were determined in the liver tissues of 15 controls and in HCC tissues of 25 patients undergoing curative hepatic resection.The patients were followed up clinically.RESULTS: Cx 26 and Cx 32 mRNAs were significantly lower in HCC tissues compared with controls (both P＜0.01). By multivariate analysis, a lower level of Cx 26 and Cx 32mRNA correlated significantly with a risk of HCC recurrence(P = 0.033) and recurrence-related mortality (P = 0.031,P = 0.031). Cx 43 mRNA was higher in HCC tissues compared with controls but did not correlate with postoperative recurrence or recurrence-related mortality. Other significant predictors of HCC recurrence included cellular dedifferentiation(P = 0.033), less encapsulation (P = 0.050), vascular permeation (P = 0.046), and daughter nodules (P = 0.046).Significant variables related to recurrence-related mortality consisted of cell dedifferentiation (P = 0.031), vascular permeation (P = 0.048), and daughter nodules (P = 0.048).The levels of Cx 26 and Cx 32 mRNAs correlated significantly with cell differentiation (P = 0.031).CONCLUSION: A low expression of Cx 26 and Cx 32 mRNAs in HCC tissues is predictive of postoperative recurrence of HCCs.