Objective To explore the effect of applying Sandwich teaching plus case based learning (CBL) methodology to nursing students having clinical internship in the department of neurology, and to provide reference for optimization of teaching method. Methods Totally, 98 nursing interns working in the department of neurology were evenly divided into 2 groups by the units where they worked. The control group received teaching with traditional methods, while the intervention group additionally received Sandwich plus CBL teaching.The two groups were evaluated with a written exam at the end of the internship block, and asked to fill out a questionnaire survey on their views of the teaching methods they received. Results The intervention group achieved high scores in end-of-block written exam and satisfaction survey regarding the teaching methods they received （P＜0.05,P＜0.01）. Conclusion Sandwich plus CBL teaching methodology helped students better grasp the required knowledge and improved teaching effect.