The purpose of this study is to explore the construction and practice of comprehensive nursing mode in neonatal intensive care unit (NICU) nursing center. By collecting and analyzing the data before and after the implementation of comprehensive nursing mode, the paper evaluates the influence of this mode on nursing efficiency, nursing quality and satisfaction of patients and their families. The results show that after the implementation of comprehensive nursing mode, nursing efficiency has been improved, nursing time and expenses have been reduced, and nursing quality and safety have been improved. Family members' satisfaction with nursing service has also been improved, and improvements in nursing quality, communication effect and medical safety have been recognized. In addition, the discharge rate of patients has improved, and the cure rate and recovery speed have also improved. The construction and practice of comprehensive nursing model provides an effective nursing service model for NICU nursing center, which is helpful to improve nursing efficiency and quality, enhance the satisfaction of patients and their families, and promote the recovery and cure of patients.