Abstract: Objective To investigate the relationship between polymorphisms of surfactant protein D (rs3088308 and rs721917) and the susceptibility to silicosis. Methods This case-control study included 125 silicosis patients and 125 individuals exposed to industrial dust but without silicosis (control group), who were strictly matched with the case group for age, gender, work type and cumulative length of dust exposure. The rs3088308 and rs721917 polymorphisms of surfactant protein-D were detected in all the participants using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The frequencies of T/T, T/A and A/A genotypes of surfactant protein-D rs3088308 locus were 22.2%, 71.2% and 5.6% in the case group, significantly different from the frequencies of 17.6%, 58.4% and 24.0% in the control group, respectively (P< 0.05). The frequencies of C/C, C/T and T/T genotypes of rs721917 locus were 17.6%, 56.8% and 25.6% in the case group, similar to the frequencies of 15.2%, 60.0% and 24.8% in the control group, respectively (P>0.05). Conclusion Surfactant protein-D rs3088308 polymorphism is significantly associated with silicosis, and the T allele may be a risk factor for silicosis in individuals exposed to industrial dust.