Alcohol-induced osteonecrosis of femoral head (ONFH) is one of the most important pathogenesis of nontraumatic ONFH. However, its pathogenesis mechanism is still unknown. Osteoprotegerin (OPG) has been implicated in multiple functions including blocking osteoclast maturation, controlling vascular calcifications, promoting tumour growth and metastasis. This study is focussed on OPG gene polymorphisms associated with alcohol-induced ONFH. A total of 509 participants (209 patients and 300 normal individuals) were recruited, and we selected 13 single-nucleotide polymorphisms (SNPs) to evaluate the association between genetic susceptibility variants and alcohol-induced ONFH by using the χ2 test and genetic model analysis. Overall, OPG SNPs (rs1485286, rs1032128 and rs11573828) were confirmed the strongest increasing risks on alcohol-induced osteoporosis of femoral head in recessive model (rs1485286: OR, 1.71; 95% CI, 1.07-2.73; P = 0.025 for T/T); (rs1032128: OR, 1.73; 95% CI, 1.08- 2.77; P = 0.022 for G/G); (rs11573828: OR, 3.89; 95% CI, 1.02- 14.85; P = 0.033 for T/T). SNP rs11573856 was considered as a protective effect to the occurrence of alcohol-induced ONFH, while adjusted for age and gender in dominant and log-additive models (rs11573856: adjusted OR, 0.60; 95% CI, 0.37- 0.96; P = 0.033 for G/A- A/A); (rs11573856: adjusted OR, 0.63; 95% CI, 0.41- 0.96; P = 0.042). We conclude that OPG gene polymorphisms were associated with the occurrence of alcohol-induced ONFH.