Abstract Purpose To evaluate the short-term effect of lamivudine (LMV) treatment for severe chronic hepatitis B. Method Patient data related to the safety and efficacy of using lamivudine (LMV) to treat hepatitis B virus (HBV)-induced liver failure or severe hepatitis were acquired from previous literature. These studies were retrieved from PubMed, Ovid, SpringerLink, Biosis Previews, Academic Search Premier, ProQuest Medical Library, Cochrane Library, China National Knowledge Infrastructure Full-text Database, VIP Chinese Scientific Journal Database, and Chinese Biomedicine. Relative risk and weighted mean difference were used to measure the effects. The major predictors observed included total bilirubin (TBIL), prothrombin activity (PTA), survival rate, and HBV-DNA negative change rate. Groups were further divided according to the clinical course and disease staging. Results A total of 242 studies were retrieved from the databases. At weeks 4, 8, and 12 of the treatment course, the survival rates and PTA of the test group were distinctively higher than those of the control group. However, TBIL concentrations in the test group were lower than the control group. The HBV-DNA negative change rate was distinctively higher throughout the 12 weeks of LMV treatment. For patients who started LMV treatment in the middle stage, the mortality rate of the test group was lower. For patients who started LMV treatment during the advanced stage, no significant difference was observed between the test and control groups. Conclusion LMV decreased HBV-DNA levels in the serum, improved liver function in patients, and enhanced survival rate during the early and medium stages of severe chronic hepatitis B.