The association of rs707921 and rs707922 SNPs in the apolipoprotein M (APOM) gene and serum lipid levels is still controversial. This study aimed to detect the association of the APOM rs707921 and rs707922 SNPs and several environmental factors with serum lipid profiles. Genotyping of rs707921 and rs707922 was performed in 703 of Mulao's and 707 of Han's participants. The serum levels of TG in Mulao, and TG and HDL-C in Han were different between the A and C allele carriers of rs707921 (P < 0.05-0.01); while the serum levels of TG in both Mulao and Han were different between the T and G allele carriers of rs707922 (P < 0.05-0.01). According to the gender-subgroup analysis, the levels of TC in Mulao females, TG and ApoB in Han males, and HDL-C in Han females were associated with the genotypes of rs707921 (P < 0.05 for each); whereas the levels of TG in Mulao males, and TG and ApoB in Han males were correlated with the genotypes of rs707922 (P < 0.05 for each). Serum lipid parameters were also associated with several environmental factors (P < 0.05-0.001). The APOM gene rs707921 and rs707922 SNPs are associated with some serum lipid parameters in the two ethnic groups, but the trends of association suggest that the two SNPs might have racial/ethnic- and/or gender- specificity.