Osteosarcoma is the most common type of bone cancer in adolescence. Bone morphogenetic protein-2 (BMP-2) plays important roles in the development of bone and cartilage and in inhibiting the tumorigenicity of cancer stem cells in human osteosarcoma cell line. The aim of this study was to examine whether polymorphisms in the BMP2 gene are associated with osteosarcoma risk and prognosis in Chinese population. Five single nucleotide polymorphisms (SNP) in the BMP2 gene were genotyped in a case-control study, including 203 osteosarcoma patients and 406 cancer-free controls. We found that rs3178250 TT genotype was associated with significant increased osteosarcoma risk (age-adjusted odds ratio (OR) = 2.06, 95% confidence intervals (CI) of 1.23-3.45) compared with CC genotype. Subjects carrying the AA genotype of rs1005464 had significant decreased cancer risk (age-adjusted OR = 0.44, 95% CI of 0.23-0.85) compared with those carrying the GG genotype. Haplotype analysis also showed that carriers of the G-T-T-G and A-T-T-G haplotypes (rs235764-rs3178250-rs235768-rs1005464) had significant increased risks of osteosarcoma (age-adjusted OR = 1.85, 95% CI of 1.28-2.66 and age-adjusted OR = 1.51, 95% CI of 1.06-2.16) compared with the G-C-T-A haplotype carriers. Besides, rs1005464 was an independent prognostic factor for osteosarcoma patients (GA vs. GG: age-adjusted hazard radio (HR) = 0.60, 95% CI of 0.36-0.99). Our data suggest that genetic mutations in the BMP2 gene are associated with osteosarcoma risk and prognosis in a Chinese population.