The interactions between single nucleotide polymorphisms (SNPs) and high body mass index (BMI) on serum lipid profiles are limited. This study was undertaken to detect the interactions of 10 SNPs and high BMI on serum lipid traits in an isolated population. A total of 978 normal BMI (< 24 kg/m2) and 751 high BMI (≥ 24 kg/m2) subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Genotypes of rs2066715, rs1044925, low density lipoprotein receptor (LDL-R) Ava||, rs2070895, rs2000813, rs1801133, rs3757354, rs505151, rs2016520, and rs5888 SNPs were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. The genotypic and allelic frequencies of rs2070895 and rs505151 were different between normal and high BMI subjects, the genotypic frequency of rs2000813 and allelic frequency of rs3757354 were also different between normal and high BMI subjects (P < 0.01). The levels of total cholesterol (TC), apolipoprotein (Apo) A1 (rs2066715); TC, low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and ApoA1/ApoB (rs2070895); triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and ApoA1 (rs2000813); TC, HDL-C, LDL-C, ApoA1, and ApoB (rs1801133); HDL-C and ApoA1 (rs3757354) in normal BMI subjects were different among the genotypes (P < 0.01). The levels of LDL-C, ApoB, and ApoA1/ApoB (rs2066715); HDL-C, ApoA1, ApoB, and ApoA1/ApoB (rs2070895); TC, HDL-C, ApoA1, and ApoB (rs2000813); TC, TG, HDL-C, LDL-C, ApoA1, and ApoB (rs1801133); TC, TG, and ApoB (rs3757354); TG (rs505151); TG and ApoA1 and ApoB (rs2016520); and TC, HDL-C, LDL-C, ApoA1, and ApoB (rs5888) in high BMI subjects were also different among the genotypes (P < 0.01). The SNPs of rs2066715 (LDL-C and ApoA1/ApoB); rs2070895 (TC, LDL-C, ApoA1, and ApoB); rs2000813 (ApoB); rs1801133 (TC, TG, and LDL-C); rs3757354 (TC and TG); rs505151 (TG, HDL-C, ApoB, and ApoA1/ApoB); rs2016520 (TG and ApoA1/ApoB); and rs5888 (TG, ApoA1, and ApoB) interacted with high BMI to influence serum lipid levels (P < 0.01). The differences in serum lipid levels between normal and high BMI subjects might partly result from different interactions of several SNPs and high BMI.