Influenza is a major threat to public health. Vaccination is an effective strategy to control influenza; however, the current inactivated influenza vaccine has mild immunogenicity and exhibits suboptimal efficacy in clinical use. Vaccine efficacy can be improved by the addition of adjuvants, but few adjuvants have been approved for human use. To explore novel and effective adjuvants for influenza vaccines, here we screened 145 compounds from food additives approved in Japan. Of these 145 candidates, we identified 41 compounds that enhanced the efficacy of the split influenza hemagglutinin (HA) vaccine against lethal virus challenge in a mouse model. These 41 compounds included 18 novel adjuvant candidates and 15 compounds with previously reported adjuvant effects for other antigens but not for the influenza vaccine. Our results are of value to the development of novel and effective adjuvanted influenza or other vaccines for human use.