To investigate the relationships between two COL2A1 single nucleotide polymorphisms (SNPs; T2088C and G4006A) and osteoarthritis (OA) in Han Chinese women. One hundred and twenty OA women and 120 control women were recruited. Genomic DNA was extracted from the whole blood. The COL2A1 polymorphisms T2088C and G4006A were analyzed by TaqMan assay. The levels of plasma N-propetide of type IIA collagen (PIIANP) and urinary C-telopeptide of type IIA collagen (CTX-II) were determined by ELISA. The level of plasma PIIANP significantly decreased in the OA group, compared with that in the control group (P<0.05), with 15.6±4.2 ng/ml (Mean±SD) in the OA group and 30.2±7.8 ng/ml in the control group. The level of urinary CTX-II significantly increased in the OA group, compared with that in the control group (P<0.05), with 201.4±10.2 ng/ml in the control group and 250.8±15.6 ng/ml in the OA group. There was no difference in the T2088C genotypes between the OA and control groups. The G4006A AA homozygous genotype significantly increased in the OA patients, when compared with that in the control women (P<0.05, χ2), with 24.2% (29/120) in the OA group and 10.0% (12/120) in the control group; The A allele accounted for 49.2% (118/240) in the OA group and 35.8% (86/240) in the control group. Among the G4006A genotypes, the plasma PIIANP level of the AA genotype (16.4±6.6 ng/ml) was significantly lower than those of the GG genotype (28.6±4.2 ng/ml) and GA genotype (21.5±8.0 ng/ml) while the urinary CTX-II level of the AA genotype (255.2±18.4 ng/ml) significantly increased, compared with those of the GG genotype (218.4±13.2 ng/ml) and GA genotype (221.2±15.6 ng/ml). The haplotype analysis shows that T-G was a protective factor for OA and that T-A was a risk factor. The AA genotype, A allele and T-A may increase the risk of OA in the Han Chinese women while T-G may protect these women from OA.