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Hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process resulting from the accumulation of sequential genetic and epigenetic alterations.An important change among them is from precancerous lesions to HCC.However, only few studies have been reported about the sequential genetic changes during hepatocarcinogenesis.To investigate the sequential genetic changes from precancerous lesions to HCC during hepatocarcinogenesis, we observed firstly molecular karyotypes of 10 matched HCC using Affymetrix single-nucleotide polymorphism (SNP) 6.0 arrays, and found chromosomal fragments with high incidence (more than 80%) of loss of heterozygosity (LOH).Then, we selected 28 microsatellite markers at some gene spanning these chromosomal fragments, and examined the frequency of LOH of 128 matched HCC and 43 matched precancerous lesions-nodules of altered hepatocytes (NAH) by a PCR-based analysis.Finally, we investigated the expression of proteins encoded by these genes in HCC, NAH and the surrounding hepatic tissues.The result of Affymetrix SNP6.0 arrays demonstrated that more than 80 % (8/10) cases had chromosomal fragment deletion on 4q13.3-35.1, 8p23.2-21.2, 16q11.2-24.3, and 17p13.3-12.Among 28 microsatellite markers selected, LOH frequencies at D8S262 for NAH and HCC were found to be the highest, 51.2% and 72.7%, respectively The positive rate of its adjacent gene CSMD1 in HCC, NAH, and the surrounding hepatic tissues were 27.3% (35/128), 75% (33/44), and 82% (105/128), respectively.In conclusion, LOH at D8S262 may be associated with an early genetic event of hepatocarcinogenesis, and a predictor for the monitor and prevention of HCC.