Background: Developing students’ metacognition awareness is a goal of university education as it can help equip students with life-long learning skills and promote holistic personal development. This study aimed to explore the effect of nursing comprehensive skill training course (NCST-C) on metacognitive awareness of nursing students in China, to provide a scientific foundation for improving metacognitive awareness.Design: A quasi-experimental two-group, matched pretest, post-test, and follow-up test.Methods: A total of 96 Junior nursing students were recruited using a convenience sampling and assigned to 2 groups by drawing lots with odd and even numbers in a nursing school at Huzhou University, China. The control group was received the traditional skill-training course. The intervention group was received training in NCST-C. Nursing students were evaluated metacognitive awareness inventory (MAI) at the baseline, 16-week, and 20-week follow-up points, respectively. A repeated-measures, two-way analysis of variance, and a simple effect test were used to compare each outcome measure of 2 groups.Results: The NCST-C resulted in a greater benefit for nursing students’ metacognition awareness and various dimensions (knowledge of cognition and regulation of cognition) in the intervention group. Combined with a simple effects test, the MAI and dimensions scores of those in the intervention groups significantly improved at 16 weeks after the baseline (F = 44.03-9.78); all P <0.01); and the sustainable effect of NCST-C lasted for 1 month after the intervention (F = 14.24-56.75, all P <0.01), which reached statistical significance (P < 0.05).Conclusions: The NCST-C was an effective course to develop metacognition awareness of nursing students,which design provides a new form of experimental course to improve metacognition awareness.Trial registration: http://www.chictr.org.cn/listbycreater.aspxRegistration number:ChiCTR2200057910. First registration date 22/3/2022