Abstract: Objective To study the HCV gene variation with time.Methods The envelope gene of the serial sera from 4 HCV infected patients were amplified and sequenced with different primers(HVR1b,HVR2a,HSP1b,HSP2a).Genotypes of the ser a were tested by RT-PCR based method and the sequencing of 5'-UTR,Core and Eregion.Results All the serial sera of 4 patients were infected by 1b and 2a genes,and genotype changing with time,the mixed infection was found in the samples during the exchanged period.The same types and sequences were found when amplified and sequenced with HVR1b,HVR2a primers,respectively,whereas differ ent types were obtained from the 1b/2a mixed samples using HSP1b and HSP2a.The nucleotide and amino acid sequences of the same genotype from the same serum of a patient changed with time.Conclusion The results indicated that HCV gene sequences varied at different levels,genotype changes at a higher level and gene sequence change at a lower level.