Omethoate is an organophosphorus pesticide that poses a major health hazard, especially DNA damage. The purpose of this study was to investigate the factors affecting telomere length in workers exposed to omethoate by analyzing the interaction between cell cycle gene polymorphism and environmental factors. The exposure group consisted of 118 workers exposed to omethoate for 8-10 years, the control group comprised 115 healthy people without occupational toxicant exposure history. The telomere length of genomic DNA from peripheral blood leucocyte was determined with real-time PCR. Polymerase chain reaction and restriction fragment length polymorphism was used to detect the polymorphisms in 53, 21 and 2 gene. The telomere length in the (CA + AA) genotypes for 21 rs1801270 polymorphism was longer than that in the CC genotype in control group ( = 0.015). The generalized linear model analysis indicated the interaction of the 21 rs1801270 polymorphic (CA + AA) genotypes and smoking has a significant effect on telomere length (β = -0.258,  = 0.085). The prolongation of telomere length in omethoate-exposed workers was associated with genotypes (CA + AA) of 21 rs1801270, and interactions of (CA + AA) genotypes and smoking factor.