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AIM: To investigate the distribution of HBV genotypes and their YMDD mutations in Guangxi Zhuang population, China, and to study the relationship between HBV genotypes and clinical types of HB, ALT, HBV DNA, HBe system as well as the curative effect of Lamivudine (LAM) on hepatitis B.METHODS: A total of 156 cases were randomly chosen as study subjects from 317 patients with chronic hepatitis B (CHB). HBV genotypes were determined by PCR-microcosmic nucleic acid cross-ELISA. YMDD mutations were detected by microcosmic nucleic acid cross-nucleic acid quantitative determination. HBV DNA was detected by fluorescence ratio PCR analysis.LAM was given to 81 cases and its curative effect was observed by measuring ALT, HBV DNA load, HBeAg, and HBeAg/HBeAb conversion rate.RESULTS: HBV genotypes B, C, D, and non-classified genotypes were found in Guangxi Zhuang population.accounting for 25.6%, 47.4%, 58.3%, and 16.0%,respectively. Seventy-four cases were CD-, CB-, BD-mixed genotypes (47.7%). Forty-six (29.5%) cases had YMDD mutations. Genotype B was mostly found in mild and moderate CHB patients. Genotypes C, D and mixed genotype mostly occurred in severe CHB cases.Genotypes D and CD HBV-infected patients had higher ALT and HBV DNA than patients with other types of HBV infection. There was no significant difference among the genotypes in YMDD mutations, clinical types, ALT and HBV DNA level. Non-classified types geno had a significantly lower positive rate of HBeAg than other genotypes (x2= 12.841, P＜0.05). There was no significant difference in ALT recovery rate, HBV DNA load, HBeAg,and HBeAg/HBeAb conversion rate, 48 wk after LAM treatment between groups of genotypes D, CD, and nonclassified type.CONCLUSION: Genotypes B, C, and D, non-classified and mixed genotype of HBV are identified in the Guangxi Zhuang population. Variations in genotypes are associated with clinical severity and serum ALT levels, but not with YMDD mutation or HBV DNA load.Therapeutic effects of LAM on clinical parameters are not influenced by differences in genotypes. Further studies are needed to gain an in-depth understanding of the relationship between HBV genotypes and serum HBeAb and HBeAg.