Objective Flipped classroom teaching mode can improve students’ academic performance and cognition, and develop students’ initiative and innovation ability, but there are obvious deficiencies in systematic knowledge mastery and education. However, the traditional teacher-centered teaching concept has its unique advantages in systematic knowledge learning and education. In recent years, there have been reports on the reform of the blended teaching mode combining flipped classroom and traditional teaching mode, but no relevant research has been carried out in the Biochemistry teaching of nursing and clinical medicine majors.Methods We introduced Biochemistry blended teaching mode based on the combination of flipped classroom with the traditional teaching mode into classes 2020 of nursing (31 students) and clinical medicine (245 students divided into 2 classes) in Cheeloo Medical School, Shandong University. Compared to traditional teaching mode for classes 2019, students’ academic performance and self-cognition were analyzed.Results Compared with traditional teaching mode, the students who received blended teaching mode achieved higher scores than those who received traditional teaching mode (P<0.01); the students’ cognition also improved significantly (P<0.01 or P<0.05). The effect of Biochemistry blended teaching mode in small class (nursing major) is better than that in large class (clinical medicine major). This study provides reference for related teaching and research in medical colleges and universities.Conclusion The blended teaching mode of Biochemistry is beneficial to the teaching reform of medical colleges.