Objective: To investigate the methylation status at the promoter region of the p16INK4a and retinoblastoma (Rb) gene in cirrhosis liver tissue and its relations with the protein expression of the two genes. Methods: The DNA methylation status and protein expression of p16INK4a and Rb in the liver tissues from 65 patients with cirrhosis and 20 healthy subjects were detected by PCR and immunohistochemical staining, respectively. Results: No abnormal methylation of p16INK4a and Rb gene was detected in any of the 20 cases of normal liver tissue, while the methylation ratios of the p16INK4a and Rb gene in the cirrhosis liver tissue were 40% (26/65) and 36.9% (24/65), respectively. The integrated optical densities (IOD) of the p16INK4a and Rb protein expression in the normal liver tissue were 225.7±27.4 and 254.7±34.8, while those in the cirrhosis liver tissue were 32.4±7.5 and 45.2±6.4, respectively, and both differences had statistical significance (both P<0.05). Conclusion: Cirrhosis liver tissue has abnormal methylation of p16INK4a and Rb gene and decreased expression of p16INK4a and Rb protein, and the resulting loss of cell cycle control may be involved in the occurrence and development of liver cirrhosis.