Genetic variants of FTO and MC4R have been linked with obesity and T2DM in populations of Europeans. In this study, we have investigated the association of FTO rs9939609 and MC4R rs17782313 with obesity and T2DM in the Chinese population and analyzed the relationship between rs9939609 and rs17782313. 2351 individuals were recruited. We tested the rs9939609 and rs17782313 by sequences retrieval method. Clinical and biochemical characteristics were measured. The rs9939609 per-A allele and rs17782313 per-C allele increases of OR for obesity was 1.42 (95% CI 1.39–3.74) and 1.39 (95% CI 1.21–3.53).The genotypic OR for obesity was 1.92 (95% CI 1.81–4.67) for AA genotype, 1.71 (95% CI 1.47–4.54) for AT genotype, 1.87 (95% CI 1.72–4.00) for CC genotype, and 1.44 (95% CI 1.20–3.18) for CT genotype. BMI of participants carrying neither FTO nor MC4R risk allele was 25.9 ± 4.9, one risk allele was 26.4 ± 5.1, two risk alleles was 28.1 ± 5.5, and there or four risk alleles was 33.2 ± 6.3. We found no association between FTO and MC4R and the Chinese population with T2DM (P > 0.05). Our data support that the rs9939609 and rs17782313 are strongly associated with obesity and BMI. Their combined effects were significant in Chinese population. No association between FTO and MC4R and Chinese population with T2DM was found.