Variants in the SMAD family member 3 (SMAD3) have recently been reported to be associated with osteoarthritis (OA) in European populations. However, the results are contestable. To assess the role of such variants in SMAD3 in OA susceptibility in peripheral joints OA, we conducted a case-control study in a Northeast Chinese population. The SMAD3 SNP was genotyped in patients who had primary symptomatic OA with radiographic confirmation and clinical symptom and in controls, and the associations were examined. A total of 111 knee OA patients, 121 hand OA patients and 236 controls were genotyped. Statistically significant difference was detected in genotype and allele frequencies between OA and control groups in the population. There were significant association for knee OA OR = 3.68 (95 % CI 2.03-6.70; p < 0.001) and for hand OA OR = 3.60 (95 % CI 2.01, 6.44; p < 0.001). The association was also positive even after stratification by sex except for male population of knee OA. Our data indicated that genetic variation in the SMAD3 gene is involved in pathogenesis of both knee OA and hand OA in Northeast Chinese population, which is consistent with in European populations.