Abstract: AIM To investigate the application of flipped classroom combined with case-based learning in instruction of high altitude cardio-cerebral lesions. METHODS A total of 80 medical students enrolled in the 5-year program were chosen as objects of analysis. They were randomly divided into control group (Class A, 40 students) in which students were divided into five groups (8/group) with traditional teaching model and experimental group (Class B, 40 students) in which the students were also divided into five groups (8/group) with flipped classroom combined with case-based learning model. At the end of the course, examinations were administered and the scores of the exams were analyzed. At the same time, a questionnaire survey was conducted for instruction evaluation. RESULTS Examination scores of class B were significantly higher than those of class A (P<0.05). The questionnaire results revealed that the flipped classroom combined with the case-based learning model was superior to the traditional teaching model. The flipped classroom combined with case-based learning was obviously better than the traditional teaching model in improving students' learning interests and independent thinking ability and enhancing their knowledge-acquiring ability. CONCLUSION The application of flipped classroom combined with the case-based learning model is not only feasible and effective in instruction of high altitude cardio-cerebral lesions but also deepens the understanding of theoretical knowledge and improves a variety of student abilities.