Abstract: Objective To evaluate the association of UCP1 gene single nucleotide polymorphisms with overweight or obesity. Methods The single nucleotide polymorphisms of UCP1 gene in 275 overweight or obese individuals and 253 normal controls were genotyped by the method of ligase detection reaction. The construction of haplotypes and their interaction analysis with relevant factors were carried out by SNPStats online. Results The weight, body mass index, total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein showed significant differences between the two groups (all P<0.05). In the recessive genetic model, subjects with genotypes (AA+AG) and GG of rs1800592 showed significant differences between overweight or obesity group and control group (P=0.048, OR = 1.154，95% CI：1.002-2.286). Haplotype analysis showed significant differences in frequency of haplotypes CTCA,CTAG,TACG between two groups (CTCA：P=0.043，OR=0.658，95% CI：0.439-0.988; CTAG：P=0.043，OR=0.658，95% CI：0.439-0.988; TACG：P=0.004，OR=0.449，95% CI：0.257-0.786). There was an interaction between haplotypes and total cholesterol (χ²=15.955，P=0.014). In the abnormal group of total cholesterol, it showed significant differences in the frequency of haplotypes CTAA, CTCG, CTCA and CTAG between two groups comparing with CTAA, in the normal group of TC (CTAA: P<0.001,OR= 2.731，95% CI：1.550-4.752; CTCG: P<0.001, OR=9.768，95% CI：3.403-28.042; CTCA: P=0.037, OR=2.713，95% CI：1.028-7.159; CTAG: P=0.037, OR = 2.713，95% CI：1.028-7.159). Conclusions In the recessive genetic mode, the genotype (AA+AG) may be a risk factor of overweight and obesity. The haplotypes CTCG, CTCA, TACG may be protective factors of overweight and obesity. When the total cholesterol is abnormal, the haplotypes CTAA, CTCG, CTCA or CTAG, may be risk factors of overweight and obesity.