OBJECTIVE To explore the relationship between genetic polymorphism of P53, P21, CCND1 and susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM). METHODS 183 workers occupationally exposed to VCM were involved in our study. Cytokinesis-block micronucleus (CB-MN) assay was used to detect chromosome damage in peripheral lymphocyte. PCR-RFLP technique was applied to detect polymorphisms in P53 gene (exon4, intron3 and intron6), P21 gene (exon2 and exon3) and CCND1 (exon4). RESULTS The risk of chromosomal damage for VCM-exposed workers with more than 30 yr was 1.2202 (95% CI: 1.0580 approximately 1.4072, P = 0.0062) compared with the younger workers, and the risk of female workers was 1.1491 (95% CI: 0.9841 approximately 1.3416, P = 0.0772) compared with male workers. The MN frequency in subjects with P53 intron6 mutant homozygous and heterozygous was higher than their wild-type homozygous counterparts (OR = 1.3032, 95% CI: 1.1285 approximately 1.6405, P = 0.0285). P53 exon4, intron3 and intron6 haplotype pairs of BBB/AAA and BAB/AAA were associated with the increased frequencies of micronucleus. CONCLUSIONS Among VCM-exposed workers, more than 30ys, female, carrying P53 intron6 mutated allele and BBB/AAA and BAB/AAA haplotype pairs have higher risk of chromosomal damage.