To improve the response to IFN-α therapy for chronic hepatitis B, researchers have been constantly dedicated to develop novel molecular technologies or optimize combination strategies based on IFN-α, such as optimizing delivery strategies of IFN-α molecules, identifying new IFN-α subtypes with stronger antiviral activity, and combining IFN-α with other therapies. This evidence concerns the gene IFNA2 and chronic hepatitis B virus infection.