Background: In the new era, medical teaching is faced with the dual tasks of knowledge transmission and value guidance. In this study, we applied CBL combined with humanistic literacy to undergraduate medical students’ internal medicine diagnostics teaching, so as to promote medical students’ better acquisition of knowledge and improvement of literacy.Methods: Fifty-six five-year undergraduate medical students from Xiangya Medical College of Central South University were randomly divided into experimental group and control group, with 28 students in each group. In the experimental group, CBL combined with humanistic literacy teaching mode was adopted, while in the control group, traditional teaching methods were adopted. The two groups were compared to explore the effect of innovative teaching mode in the course of medical diagnostics. Result: The scores of multiple choice questions and comprehensive analysis questions of the experimental group were significantly higher than those of the control group. The teaching satisfaction survey of the two groups of students shows that the students in the experimental group are significantly higher than the control group. In addition, the comprehensive ability questionnaire survey showed that the experimental group of students compared to the control group of students, this group of students believed that the innovative teaching mode of CBL combined with humanistic literacy could significantly improve humanistic literacy, learning motivation, independent thinking, clinical thinking, teamwork, clinical communication and other abilities ( P<0.05) .Conclusion: Under the background of new medicine, CBL combined with humanistic literacy teaching mode is obviously superior to the traditional teaching mode in improving the professional knowledge level and cultivating the comprehensive quality and ability of undergraduate medical students. This teaching mode can not only improve the teaching quality, but also improve students’ learning ability, exercise their learning enthusiasm, and improve students' happiness in learning.