Abstract： Objective To investigate the mutations of the mismatch repair genes hMLH1 and hMSH2 in hereditary nonpolyposis colorectal cancer(HNPCC).Methods The DNA samples of 76 probands of HNPCC families underwent PCR amplification and sequencing on 35 exons in hMLH1 and hMSH2 genes.Results (1)The overall mutation rate of the hMLH1 and hMSH2 genes was 33%(25/76).(2)22 mutations were found,16 in the hMLH1 gene and 6 in the hMsH2 gene.(3)The spectrum of mutation type included franle shift,nonsense,splice site,and misserlse mutations.Missense mutation was the most coinnlon mutation type.Condusion The hMLH1 and hMSH2 mutations in Chinese HNPCC families show a wide spectrum.It seems that hMLH1 gene iS involved more frequently than hMSH2 gene.A certain number of HNPCC families Can be benefited from the genetic screening for mutation of the mismatch repair genes.