Airworthiness regulations are key for guaranteeing the safety of civil aviation products and a significant indication of a nation’s aviation power. A well-developed airworthiness regulation system is an effective technical and management means by which a country with an advanced aviation industry ensures the safety of its civil aviation products and occupies the broadest market share while using International Civil Aviation Organization (ICAO) rules. As major national science and technology projects for large aircraft, aero-engines, and gas turbines are implemented, it is imperative for China to further improve its airworthiness regulation system. In this study, we clarify the implications of aero-engine airworthiness regulations and summarize the problems regarding aero-engine airworthiness regulations both in China and abroad. Based on this, the formation strategy and technical path for the next-generation airworthiness regulations of aero-engines are explored from the perspectives of ICAO and China’s civil aviation industry. The formulation strategy emphasizes the requirement for system safety, and specific principles include an equivalent level of safety, clear logic, international compatibility, and local applicability. Moreover, a new top-level framework for the aero-engine airworthiness regulations is proposed; it inherits the international lessons learned, ensures a high safety standard, and adapts to the progress of system safety technologies of aero-engines. Furthermore, we suggest that China should continuously deepen the research, simultaneously expand application, and coordinate industry development, thus to promote the construction of the aero-engine airworthiness regulation system in China.