Objective To explore the effect of a program combining rain classroom with virtual reality simulation for teaching the course of Fundamental Nursing. Methods Fifty-five nursing students in Class one of Grade 2017 were treated as the intervention group and received teaching by employing rain classroom and virtual reality simulation. Their counterparts in Class two (n=59) were served as the control group and subjected to conventional teaching. After completion of the course, self-directed learning ability, performance in the test, teachers′ and students′ evaluation of the teaching were compared between the two groups. Results The intervention group had higher theoretical and experimental performance as well as higher self-directed learning ability compared with the control group (P＜0.05 for all). Evaluation of the teaching from the other teachers presenting in the class was also higher in the intervention group than the control group (P＜0.05,P＜0.01). More than seventy percent (74.5%-92.7%) of the students in the intervention group positively appraised the new teaching method. Conclusion Combining rain classroom with virtual reality simulation for teaching realizes online and offline teaching as well as achieves classroom informatization, thus to improve students′ self-directed learning ability and teaching effect.