Multiple lines of evidence have suggested that genetic factors may contribute to steroid-induced osteonecrosis of the femoral head (SONFH). Complement receptor 2 (CR2), constituting a family of regulators of complement activation, has been recently reported to be associated with osteonecrosis of the femoral head (ONFH) in Koreans. The aim of this study was to evaluate the relationships between polymorphisms of the gene and susceptibility to SONFH in the male Han Chinese population. A total of 468 SONFH patients and 1224 healthy controls were recruited for this study. Ten tag single nucleotide polymorphisms (SNPs) located within the gene were genotyped. Genetic association analyses, including SNP and haplotypic analyses, were performed for the 10 SNPs. Furthermore, bioinformatic analyses were conducted to examine the functional consequences of SNPs shown to be significantly associated with SONFH. An intronic SNP, rs311306, was identified to be significantly associated with the risk of SONFH ( = 0.0008, odds ratio = 1.44). Allelic analyses showed that the C allele of this SNP significantly elevated the risk of SONFH, which was replicated in genotypic association analyses. Moreover, a 3-SNP haplotype was significantly associated with SONFH (rs311306-rs17044576-rs3767933,  = 7.49 × 10). Furthermore, bioinformatic analyses indicated limited functional consequences of SNP rs311306, but a complex interaction network was constructed for the protein encoded by the gene and proteins encoded by the , , and genes. Our findings shed new light on the link between the gene and SONFH in Han Chinese males, providing clues as to the nature of the mechanisms involved in the etiology of ONFH.