In this study, 897 surgical instruments used for comprehensive management of hand supply from January to December 2019 were selected as the control group. Similarly, 1086 surgical instruments administered with 6Sigma from January to December 2020 were selected as the observation group. By observing and comparing the differences between the two groups of patients in the operating room equipment cleaning pass rate and general indicators, other related pass rate, operating room equipment defects, and doctors' satisfaction with equipment, to explore the application value and influence of comprehensive nursing in operating room and disinfection supply center combined with 6Sigma management in operating room equipment management. The results show that the application of hand-supply integration combined with 6Sigma management has a good effect on operating room equipment management, which significantly improves the qualified rate of operating room equipment cleaning and the satisfaction of doctors to the equipment, and reduces the defects of operating room equipment, which has a certain reference value for operating room equipment management.