OBJECTIVE: To explore the effect of occupational lead exposure on the relative telomere length(RTL) and mRNA expression of telomere-binding protein POT1-interacting protein 1(TPP1) in peripheral blood of workers. METHODS: A total of 303 workers exposed to lead were selected as the exposure group and 72 administrative logisticians personnel in the same factory as the control group using the simple random sampling method. Their peripheral blood samples were collected and were used to detect the blood lead level by Graphite furnace atomic absorption spectrometry. RTL and the relative expression of TPP1 mRNA by real-time quantitative polymerase chain reaction. RESULTS: The blood lead level of the exposure group was higher [Media(M): 68.2 vs 266.1 μg/L, P<0.01], the RTL was shorter(M: 0.96 vs 0.70, P<0.01), and the relative mRNA expression of TPP1 was lower(M: 0.92 vs 0.51, P<0.01) compared with the control group. Spearman correlation analysis results showed that the blood lead level were both negatively correlated with RTL [Spearman correlation coefficient(r_S) =-0.18, P<0.01], and the relative mRNA expression of TPP1(r_S=-0.19, P<0.01), while the RTL was positively correlated with the risk of RTL shortening and the relative mRNA expression of TPP1 decline was increased in lead exposure(P<0.01). CONCLUSION: Lead exposure can shorten the RTL and reduce the relative mRNA expression of TPP1 in workers. The mechanism may be that lead interferes with telomere repair process by inhibiting the mRNA expression of TPP1.