Objective To investigate the association between gallstones (GS) and metabolic syndrome (MS) in southern Xinjiang, China, and to provide experience for the prevention and control of metabolic diseases in southern Xinjiang. Methods The patients with GS who visited First Division Hospital, Second Division Korla Hospital, and Third Division Hospital of Xinjiang Production and Construction Corps from March 2015 to March 2019 were enrolled as case group, and cluster sampling was used to select the individuals who underwent physical examination in Third Division 51st Regiment Hospital during the same period of time were enrolled as control group. According to inclusion and exclusion criteria, 1140 cases were enrolled in each group after 1∶ 1 matching based on age and sex. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for GS. Dummy variables were included by logistic regression to evaluate multiplicative interaction between MS components, and the parameter estimate and covariance matrix of the logistic regression model and interaction calculation table were used to calculate and evaluate additive interaction between MS components. Results The risk of GS in MS patients was 2.33 times that in non-MS patients (odds ratio [ OR ]=2.33, 95% confidence interval [ CI ]: 1.86-2.92). In addition, the components of MS also increased the risk of GS, including blood glucose ( OR =2.94, 95% CI : 2.36-3.68), blood pressure ( OR =1.50, 95% CI : 1.26-1.80), blood lipids ( OR =1.48, 95% CI : 1.25-1.75), and body mass index ( OR =1.44, 95% CI : 1.21-1.70). After adjustment for multiple factors, the risk of GS gradually increased with the increase in the number of metabolic abnormalities, i.e., one abnormality ( OR =1.55, 95% CI : 1.22-1.99), two abnormalities ( OR =2.13, 95% CI : 1.66-2.72), three abnormalities ( OR =3.48, 95% CI : 2.59-4.69), and four abnormalities ( OR =4.65, 95% CI : 2.79-7.84). No additive or multiplicative interaction was found between MS components. Conclusion GS is closely associated with MS in southern Xinjiang, and the risk of GS gradually increases with the increase in MS components. No additive or multiplicative interaction is found between GS and MS components.