Objective To investigate the effect of gut bacteria under chronic colitis on the progression of hepatoma in mice. Methods 22 hepatitis B virus (HBV)-transgenic mice (male, 8 weeks) were randomly divided into two groups, one group (n=10) was fed the drinking water containing 2% dextran sodium sulphate(DSS)to induce chronic colitis and the control group(n=12)was fed with normal drinking water. In order to investigate the effect of gut microbes, 7 male HBV-transgenic mice(8 weeks, with no detectable hepatoma under microscopy) were cohoused with 4 mice with hepatoma for 16 weeks. Results No significant liver cell damage was observed in the group of the mice fed with 2% DSS-containing drinking water. By the 22-week old, 9 of the 10 mice(90.0%) fed with 2% DSS-containing drinking water, 2 of the 12 mice(16.7%) fed with normal drinking had hepatoma. Both the hepatoma incidence and the tumor numbers in the group of mice fed with DSS-containing water were significantly higher than that in the controls (P=0.002 and P=0.028respetively). Compared to controls, the bacteria family Prevotella (P=0.022) and Anaeroplasma (P=0.014) reduced significantly in the mice with induced chronic colitis. All the mice (n=7) cohoused with the mice with hepatoma had the liver tumor developed at 24-week-old. Conclusion Alterations of gut bacteria under chronic colitis may promote the development of liver cancer.