Objective To explore the relationship between psychological control locus and academic self-efficacy of undergraduates majoring in preventive medicine, and to provide reference for improving the learning quality of undergraduates majoring in preventive medicine. Methods In April 2021, 220 undergraduates of preventive medicine enrolled from 2016 to 2020 by a medical university in Xinjiang were surveyed by the Chance Scale and academic self-efficacy Scale. The data were analyzed by t-test and Pearson correlation. Results A total of 186 students participated in this study. The scores of three dimensions as internal control, chance and powerful others of control locus were 32.25±4.72, 25.56±6.19 and 25.23±6.80 respectively. The total score of undergraduates' academic self-efficacy was 71.78±11.37 and the scores of learning ability self-efficacy and learning behavior self-efficacy were 37.25±7.12 and 34.54±5.63 respectively. Male students' score (26.94±6.39) was significantly higher than female students (24.14±6.85) on the dimension of powerful others (P=0.006). The Pearson correlation coefficients between the internal control dimension and academic self-efficacy, learning ability self-efficacy and learning behavior self-efficacy were 0.343, 0.304 and 0.309 respectively (all P<0.001); The Pearson correlation coefficients between the two dimensions of powerful others and chance and the dimension of self-efficacy of learning ability were -0.208 (P=0.004)and -0.232(P=0.001) respectively. Conclusions More male students believe that the authority may control their life more than female students,teachers should pay attention to the role of female students in driving male students. The internal control dimension of undergraduates' of control locus is positively correlated with academic self-efficacy,so we can improve undergraduates' academic self-efficacy by enhancing their self-confidence of controlling their life.