Objective To analyze the effect of implementing systematic operating room nursing cooperation in infantile cleft lip and palate repair surgery during perioperative period. Methods A total of 62 children who underwent infantile cleft lip and palate repair surgery in our hospital from October 2022 to October 2024 were selected as the research subjects. According to the different nursing methods, they were divided into reference group and study group, with 31 children in each group. The reference group was given conventional nursing, and the study group was given systematic operating room nursing. The anxiety degree, cooperation degree during anesthesia induction period, complications, nursing satisfaction and clinical related indexes were compared between the two groups. Results The scores of all dimensions of anxiety degree in the study group after nursing were lower than those in the reference group (P <0.05). The cooperation score during anesthesia induction period in the study group after nursing was lower than that in the reference group, and the proportion of scores above 5 was lower than that in the reference group (P <0.05). The incidence of complications in the study group (3.23%) was lower than that in the reference group (19.35%) (P <0.05). The nursing satisfaction rate in the study group (100.00%) was higher than that in the reference group (83.87%) (P <0.05). The operation time and extubation time in the study group were shorter than those in the reference group, and the VAS score after nursing was lower than that in the reference group (P <0.05). Conclusion The application of systematic operating room nursing cooperation in infantile cleft lip and palate repair surgery during perioperative period is effective, which can effectively reduce the anxiety degree of children, improve the cooperation degree during anesthesia induction period, reduce the incidence of complications, improve the parental satisfaction degree, shorten the operation time and extubation time, alleviate the postoperative pain, and have positive significance in promoting the rapid rehabilitation of children.