In the field of cloud-edge collaborative industrial control system protection for petroleum and petrochemical enterprises, systems generally face risks of autonomous control, unknown attacks, and sustained stable operation. Enterprises urgently need to improve the design and evaluation of existing industrial control system cybersecurity protection architectures, and enhance key technologies and components to ensure the safe and stable operation of their industrial control systems. Based on the mainstream protection architecture of Defense-in-Depth network security , in accordance with the improvement idea of "support components-equipment-system-evaluation", we integrate the technologies of Endogen ous Cybersecurity based on self-controllable, redesign the architecture of key components such as dynamic heterogeneity, multi-mode arbitration, and quadruple control, realize the key supporting components of mimetic MCU, safety PLC, and safety DCS, build a new type of industrial control system security isolation gateway and cloud-edge intelligent platform, and finally realize the construction of a new type of industry-al control system intelligent protection system with cloud-edge collaboration. A digital twin testing platform was built based on real-world petroleum and petrochemical production scenarios, incorporating real production data. Testing was conducted using both quantitative cybersecurity effectiveness assessments and attack verification assessments. The effectiveness quantitative assessment achieved a 100% compliance rate, while the attack verification assessment achieved a 99% attack defense success rate. Compared to the traditional defense model before the improvements, the system''s protection capabilities have been significantly improved. The new industrial control system security protection design based on Endogenous Cybersecurity has significantly improved the system protection capability under the current network security situation, providing a feasible, advanced and efficient solution for the security improvement of industrial control systems in the petroleum and petrochemical industries.