Chemotherapy drugs are high-risk medications, and medication and occupational safety are important indicators in the new method of hospital accreditation. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach in our unit that was established in 2015. The motivation for improvement was based on an analysis of the current status, in which the correctness of the cognition of administration of HIPEC is 55.2%, and the correctness of the safety of chemotherapy administration was only 50.4%. Solutions have been established to create a standard operation procedure for nursing care during HIPEC administration, including a splash prevention kit for chemotherapy treatment, an audit system, and in-service education training. After implementing this specific project for improvement, the correctness of the cognition was increased from 55.2% to 100%, and the correctness of the safety of chemotherapy administration improved from 50.4% to 100%, both of which reached the project's goal. This project is expected to increase the awareness of occupational safety during the administration of chemotherapy drugs in medical institutions.