Abstract: Objective To investigate the performance of baseline Anti-HBc as a predictor for HBeAg seroconversion in chronic hepatitis B（CHB） patients treated with Peginterferon Interferons α-2a （Peg-IFNα-2a） sequentially after Entecavir （ETV） treatment for 96 weeks. Method 103 CHB cases treated with ETV singly were included into this study and divided into control group and experimental group randomly. Among those, 56 cases in experimental group received sequential treatment of Peg-IFNα-2a on the basis treatment of ETV for 12 weeks, then treated with Peg-IFNα-2a alone; 47 cases in control group treated with ETV alone continuously. For all patients, examination of blood routine, thyroid and liver functions were performed every 12 weeks; meanwhile, the levels of HBsAg, Anti-HBs, HBeAg and Anti-HBe were detected by electrochemiluminescence assay, the level of Anti-HBc was detected by ELISA, the level of HBV DNA was detected by fluorescent quantitative PCR; and the HBeAg seroconversion rate and HBsAg disappearance rate of CHB were compared between the two groups after 48 weeks treatment. Results After treatment for 12 weeks, the median of HBsAg level in the control group was relatively stable, and decreased in experimental group. After treatment for 48 weeks, compared with the control group, the rates of HBeAg seroconversion and HBsAg disappearance in the experimental group both increased. Conclusion Baseline Anti-HBc for fixed quantity of HBsAg can be used as an index for predicting the curative effect, and observe the long term efficacy.