Objective To investigate the polymorphic loci of four candidate genes of ossification of posterior longitudinal ligament (OPLL) patients in the Han population in China, so as to study the loci associated with diseases. Methods The Sequenom system was adopted to analyze the 19 SNP of the four candidate genes (namely, COL6A1, BMP-2, VDR and Runx2) in 180 Han individuals, with 78 in the pathological group and 102 in the control group. The genotype distributions and allele frequencies of each SNP were compared between the two groups, and the polymorphic loci related to OPLL and their relationship were analyzed. Results Allelic analysis found no disease related locus in the 19 SNP loci of the four candidate genes. However, the genotyping analysis found that rs1321075 and rs12333172 of Runx2 were significantly different between the two groups (P=0.0339, P=0.0428), both loci were on the No.6 chromosome and Linkage Disequilibrium (LD) analysis showed linkage disequilibrium between them. The 11 SNP loci on the No.6 chromosome formed two blocks, with the range being 51 kb and 21 kb, respectively. One of the two blocks was a haploid (CTCG) made up of rs967588, rs16873379, rs3749863 and rs6908650, with a patient/control ratio of 1.75 and a risk rate of 0.81, indicating the possibility of increased incidence rate, but with no significant difference (P=0.259). No polymorphic loci were found associated with diseases for COL6A1, BMP-2 and VDR genes. Conclusion This is the first report that SNP variation of Runx2 gene may be a reason for OPLL in the Han population in China, and there was no notable connection between the polymorphic loci of COLA1, BMP-2 and VDR and OPLL.