Objective To develop an educational game to improve the emergency preparedness of adolescents for major infectious diseases, and to evaluate its preliminary application effect. Methods Based on the Information-Motivation-Behavior theory, the core content, design and production script of the educational game were determined according to literature review, brainstorming and Delphi expert consultation methods. Then the educational game was used in 285 nursing students enrolled in a technical secondary school in 2020, for 4 weeks. Results An educational game software named 《Nationwide Fight Against The Epidemic》 for emergency preparedness of major infectious disease was formed, which was consisted of three modules: game module, knowledge corner and evaluation management module. After the game intervention, the students′ awareness rate of most emergency related knowledge and skills of major infectious disease were significantly higher than those before the intervention, and the availability rate of the students′ emergency literacy was significantly higher than those before the intervention (P＜0.05, P＜0.01). Conclusion 《Nationwide Fight Against The Epidemic》 provides an innovative gamification education mode for adolescents′ emergency preparedness education of major infectious diseases, which can effectively improve adolescents′ knowledge, skills awareness and emergency literacy related to major emergency infectious diseases. It is conducive to conducting huge-scale infectious disease education effectively.