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Background: Chronic periodontitis (CP) is a multifactorial complex periodontal disease involving immune response, inflammation, alveolar bone resorption, and attachment loss. Colony stimulating factor-1 (CSF-1) controls the production, differentiation, and function of macrophages and plays a vital role in the innate immune response to the external microbial infections, suggesting the potential role of CSF-1 in the pathogenesis of periodontitis. The objective of this study is to determine the association of single nucleotide polymorphisms (SNPs) rs333967, rs2297706, and rs1058885 with CP in the Han Chinese population., Methods: Genomic DNA was isolated from buccal epithelial cells obtained from unrelated Chinese participants (440 patients with CP and 324 controls). The SNPs were genotyped by a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method., Results: Three previously identified SNPs were genotyped in Han Chinese with Shanghai origin, but none of them was statistically significantly associated with CP. However, a T-C-G haplotype in male participants showed an observed P value of 4.52(E-08), with an odds ratio of 0.092., Conclusion: None of the individual SNPs among rs333967, rs2297706, and rs1058885 in CSF-1 was found statistically significantly associated with CP in the Han Chinese population with Shanghai origin, whereas a haplotype T-C-G showed an observed statistically significant association with decreased risk of CP susceptibility in males.