OBJECTIVE： To observe the clinical efficacy of entecavir combined with intervention in the treatment of liver cancer patients with HBV DNA-negative hepatitis B. METHODS： 100 liver cancer patients with HBV DNA-negative hepatitis B were randomly divided into observation group and control group， 50 cases in each group. Control group received intervention， percutaneous puncture of  femoral artery， then injected Pirarubicin hydrochloride for injection + lipiodol in parent artery until blood stagnation， and also conventional liver protection therapy was conducted； observation group additionally received 1 mg Entecavir tablet， qd， for continuous 6 months. Clinical efficacy， HBV DNA quantification， Child-Pugh score and liver function indexes in 2 groups were compared. RESULTS： The total effective rate in observation group was 44.0％， which was significantly higher than control group （26.0％）， the difference was statistically significant （P＜0.05）. There were no significant differences in HBV DNA quantification， Child-Pugh score and liver function indexes between 2 groups （P＞0.05）. After treatment， HBV DNA quantification， Child-Pugh score， fetoprotein， alanine aminotransferase，  total bilirubin and aspartate aminotransferase significantly decreased in observation group， the differences were statistically significant compared with control group （P＜0.05）. CONCLUSIONS： Entecavir combined with intervention can obviously improve the clinical efficacy and liver function indexes of liver cancer patients with HBV DNA-negative hepatitis B.