The estrogen receptor 1 (ESR1) and Chromosome 6 Open Reading Frame 97 (C6orf97) gene polymorphisms were earlier reported to be associated with osteoporosis in the European cohort. The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNP) with bone mineral density (BMD), fracture, vertebral fracture, bone turnover or 25-hydroxyvitamin D [25(OH)D] in 1,753 randomly selected postmenopausal women in China. Vertebral fracture, BMD of lumbar spine (2-4), femoral neck and total hip were measured respectively. Serum N-terminal procollagen of type 1 collagen (P1NP), β-isomerized type I collagen C-telopeptide breakdown products (β-CTX) and 25(OH)D3 were also determined. Binary logistic regression revealed significant associations between fracture risk with rs1999805 (P=0.041, OR 1.633, 95%CI 1.020-2.616) and rs6929137 (P=0.005, OR 1.932, 95%CI 1.226-3.045) in recessive model. Significant association was also observed between vertebral fracture risk and rs1038304 (P=0.039, OR 0.549, 95%CI 0.311-0.969) in recessive model. Liner regression analyses showed that only the CC group of rs4870044 was significantly associated with total hip in dominant model (P=0.034). Our findings suggest that ESR1 and C6orf97 gene polymorphism is associated with fracture and vertebral fracture risk in Chinese postmenopausal women.