As a key regulator of insulin secretion and metabolism of glucose, cholesterol and fatty acid, hepatocyte nuclear factor 4alpha (HNF4A) was suggested as a candidate gene for type 2 diabetes (T2D); however, no association study between HNF4A and T2D in the Chinese population has been conducted before. To address this issue, we evaluated the impact of the HNF4A variants (rs1884614 and rs2425637) on T2D and metabolic traits in 1912 unrelated patients and 2041 control subjects in the Chinese Han population. Our results suggested that no individual single nucleotide polymorphisms of HNF4A was significantly associated with T2D at either allele or genotype level. However, rs2425637 in the promoter region of HNF4A was found to have an effect on total cholesterol and high-density lipoprotein before multiple testing correction. To summarize, our investigation did not confirm the effects of HNF4A variants (rs1884614 and rs2425637) on T2D risk, but found that the risk HNF4A contributed to T2D might be population specific.