Objective To investigate the clinical value of alanine aminotransferase (ALT) normalization in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) after antiviral therapy. Methods A total of 255 HBeAg-positive CHB treatment-naive patients admitted to our hospital from December 2013 to November 2016 were collected. According to laboratory testing, the upper limit of normal (ULN) for ALT levels was 42 IU/L; following the recommendations of the 2016 American Association for the Study of Liver Diseases (AASLD) CHB guidelines, the ULN for men and women were 30IU/L and 19IU/L, respectively. Patients were divided into the ALT normalization group and the ALT non-normalization group based on these two criteria, and the changes in virological and serological levels after one year of treatment and factors influencing the occurrence of hepatocellular carcinoma (HCC) during the five-year follow-up were analyzed. Results According to the laboratory criteria, 255 HBeAg-positive CHB primary patients had 212 ALT reversions and 43 non-reversions at 1 year of treatment. the HBV DNA conversion rate and HBeAg serologic conversion rate in the ALT reversion group were significantly higher than those in the ALT non-reversion group (P＜0.05). According to the criteria of AASLD guideline, at 1 year of treatment, there were 113 cases of ALT reversion and 142 cases of non-reversion. The HBV DNA conversion rate of the ALT reversion group was significantly higher than that of the ALT non-reversion group (P＜0.05).The 5-year follow-up found that 14 cases of HCC had occurred. According to the laboratory criteria and the criteria of AASLD guideline, the incidence rate of HCC in the ALT reversion group was 3.8% and 1.8%, which was significantly lower than that of the ALT non-reversion group (P＜0.05).The incidence rate of HCC in the ALT reversion group was 3.8% and 1.8%, respectively, lower than 14.0% and 8.5% in the ALT-unreformed group (P＜0.05). Logistic regression analysis was performed to analyze the relevant risk factors that might affect HCC, and univariate analysis showed that age＞40 years, cirrhosis, and ALT reversion by laboratory criteria and AASLD guideline criteria at 1 year of treatment were risk factors for HCC, and multivariate analysis showed that cirrhosis was an independent risk factor for HCC. Conclusion ALT normalization has predictive value for disease progression and clinical outcomes in CHB patients, and early ALT normalization during antiviral treatment can reduce the risk of HCC occurrence