Objective To explore association of apolipoprotein B (ApoB) gene rs676210 and rs2854725polymorphisms with gallstone disease and differences of polymorphisms between Uygur population and Han population. Methods A case control study was used. One hundred and eighty-nine patients with gallstone disease from 2010 to 2014 in our hospital were collected, of which 99 cases of Uygur population and 90 cases of Han population. One hundred and ninety age- and sex-matched healthy volunteer accepted physical examination in our hospital over the same period were collected as control, of which 93 Uygur population and 97 Han population. The ApoB genotyping of DNA samples were amplified by using SNaPshot single nucleotide polymorphism (SNP). The differences of polymorphisms between Uygur population and Han population and between patients with gallstone disease and healthy volunteer were analyzed. Results ① The differences of ApoB gene rs676210 and rs2854725 allele frequencies were not found between the patients with gallstone disease and healthy volunteer whether Uygur population or Han population (Uygur population: rs676210:χ2=0.229,P=0.633; rs2854725:χ2=0.028,P=0.866. Han population: rs676210:χ2=0.608,P=0.435; rs2854725:χ2=2.673,P=0.102). ② The differences of ApoB gene rs676210 and rs2854725 allele frequencies were not found between Uygur population and Han population whether the patients with gallstone disease or healthy volunteer (Patients with gallstone disease: rs676210:χ2=0.103,P=0.748; rs2854725:χ2=3.139,P=0.076. Healthy volunteer: rs676210:χ2=0.000,P=0.990; rs2854725:χ2=2.673,P=0.102). ③ The differences of ApoB gene rs676210 and rs2854725 genotype frequencies were not found between the patients with gallstone disease and healthy volunteer whether Uygur population or Han population (Uygur population: rs676210:χ2=2.301,P=0.317; rs2854725:χ2=3.040,P=0.219. Han population: rs676210:χ2=4.909,P=0.086; rs2854725:χ2=0.107,P=0.744). ④ The differences of ApoB gene rs676210 and rs2854725 genotype frequencies were not found between Uygur population and Han population patients with gallstone disease (rs676210:χ2=0.235,P=0.899; rs2854725:χ2=3.630,P=0.057). The difference of ApoB gene rs676210 genotype frequency was not found between Uygur population and Han population with healthy volunteer (χ2=1.026,P=0.599). While the difference of ApoB gene rs2854725 genotype frequency was found between Han population and Uygur population with healthy volunteer (χ2=9.153,P=0.010). When it was compared in pairs,α=0.05/3=0.016, the difference of G/T and T/T frequencies was found between Uygur population and Han population (χ2=6.128,P=0.013), G/T of Han population (27.8%) was higher than that of Uygur population (12.9%). Conclusions ApoB gene rs676210 and rs2854725 polymorphisms are not associated with gallstone disease. For healthy volunteer, ApoB gene rs676210 polymorphism shows no ethnics-specific difference between Uygur population and Han population, but ApoB gene rs2854725 polymorphism mightbe show a difference between Uygur population and Han population. Larger sample sizes and multicenter study are needed to confirm it.