Objective To explore the application effect of virtual-real integration teaching in the course of Comprehensive Nursing Skill Training. Methods Firstly，the teaching method was developed based on clarifying teaching methods，building a teaching resource library，constructing a teaching implementation plan，and designing teaching evaluation contents. Then，61 nursing undergraduates from the 2020 grade of a university were selected as research participants. They received virtual-real integration teaching in the course of Comprehensive Nursing Skill Training，which included stages of single skill training and comprehensive skill training. After the course，data was collected on the number of visits to the virtual simulation experiment platform and the duration of virtual simulation experiment training. Additionally，students’ course grades were analyzed，and students were invited to complete a satisfaction survey regarding the Comprehensive Nursing Skill Training course to assess their overall satisfaction. Results Among the 61 nursing students，49 accessed the virtual simulation experiment platform between 16 and 20 times. The average duration of virtual simulation experiment training was 138~272（203.43±28.67） minutes，and the average course grade was（89.66±2.91） points. About 98.3%（58/59） of the students were satisfied or very satisfied with the overall course，and those who were satisfied or very satisfied with the experimental teaching process，teaching methods，teaching design，assessment methods，and classroom participation accounted for 96.6%（57/59），98.3%（58/59），96.6%（57/59），91.5%（54/59），100%（59/59），and 98.3%（58/59），respectively. Conclusion The combination of virtual and practical teaching shows positive effects in the course of comprehensive nursing skill training. Such method helps to improve students’ course grades，and satisfaction with the course and worth promoting.