Influenza viruses are highly variable and transmissible, often causing seasonal influenza outbreaks worldwide. The genomic sequence, protein structure and function, and the viral packaging mechanism have been extensively studied and well characterized, positioning influenza viruses as key models for the identification and validation of conditionally controlled genetic elements. With the development of reverse genetics and synthetic biology, genetically engineered influenza viruses can more effectively control virus replication, thereby increasing vaccine safety and inducing a robust immune response in the host. In addition, engineered influenza viruses have garnered extensive attention in the field of tumor immunotherapy. Here, we describe methods for genetically engineering the H1N1 strain WSN on the basis of the influenza A virus reverse genetic system and provide detailed insights and perspectives on their applications.