As DNA repair associated gene, NBS1 plays a key role in the repair of DNA double strand breaks and the maintenance of genomic stability. It has been shown in recent studies some common NBS1 variants maybe associated with genetic susceptibility of tumors. In the present study, rare allele frequency of single nucleotide polymorphisms (SNPs) of NBS1 gene in primary liver cancer were detected by the method of high resolution Single Strand Conformation Polymorphism (SSCP) analysis, with the aims to analyze the correlation between NBS1 SNPs and primary liver cancer, and evaluate the applicability of the high resolution SSCP technique in the genotyping of SNPs. The rare allele frequency of NBS1 SNPs were detected in 327 cases of primary liver cancer and 295 negative controls from Han people of China by the method of high resolution SSCP analysis. The correlation was analyzed between NBS1 SNPs and primary liver cancer. Genotyping of six common NBS1 SNPs in part samples was carried out by both SSCP analysis and direct sequencing simultaneously to compare the difference between them and evaluate the accuracy and applicability of SSCP analysis in genotyping of SNPs. The results from the tissue samples showed, among six NBS1 SNPs(102G>A, 320+208G/A, 553G>C, 1197T>C, 2016A>G and 2071-30A>T), the rare allele frequency of NBS1 SNP 1197T>C was significantly higher in the 119 cases of primary liver cancer (68.1%) than that in the 95 controls of cirrhosis/chronic hepatitis B (57.9%)(P=0.0298). Similar results was obtained by detection with blood samples of 208 cases of hepatocellular carcinoma(66.8%) and 200 cases of health controls(58.8%)(P=0.0170). There was no any significant difference of the rare allele frequency of the other five NBS1 SNPs. The same result was observed for genotyping of NBS1 SNPs either by the high resolution SSCP analysis or by the direct sequencing. However, higher quality of PCR products is requested for the direct sequencing compared with SSCP analysis. These results suggest that the NBS1 SNP 1197T>C may be associated with the risk of primary liver cancer in the Chinese Han population. High resolution SSCP analysis, with the same accuracy as direct sequencing in the genotyping of NBS1 SNPs and easier to handle, is suitable for the genotyping of multiple known SNPs in large scale cohort study.