Objective To explore and evaluate the influencing factors on medical students' professionalism development based on a structural equation model so as to advance the professionalism development of medical students. Methods A total of 606 undergraduates majoring in clinical medicine, nursing and stomatology from 2015 to 2019 in Shantou University Medical School were selected as the research objects to identify seven influencing factors on self-perception of professionalism development. IBM SPSS 26.0 and AMOS 24.0 were used for data analysis and model construction. Results The scores of curriculum satisfaction, peers' communication, self-efficacy, clinical practice, teachers' professionalism, social environment assessment and academic burden were (50.28±7.26), (28.53±3.78), (15.53±2.88), (35.30±4.63), (35.04±4.73), (10.72±4.08) and (18.75±4.40) respectively. Curriculum satisfaction (β=0.36,P＜0.001),peers' communication (β=0.36,P＜0.001), self-efficacy(β=0.18,P=0.002) and clinical practice (β=0.13,P=0.011) are the direct positive influence factors to medical students' professionalism. Teachers' professionalism (β=0.30,P＜0.001) plays an indirect positive role through mediating factors of curriculum satisfaction and clinical practice. Social environment assessment (β=-0.16,P＜0.001) plays an indirect negative role through the mediating factors of peer communication and curriculum satisfaction. Academic burden (β=-0.09,P＜0.001) plays an indirect negative role through the mediating factors of self-efficacy and peer communication. Conclusions Course satisfaction, peer communication, self-efficacy and clinical practice are the direct and positive influencing factors of medical students' professionalism; teacher quality is the indirect positive influencing factor; social environment evaluation and academic burden are indirect negative influencing factors. Implementing reform measuresaccording to the role path of the 7 influencing factors in this study, can promote medical students' professionalism.