Despite extensive efforts to improve the effectiveness of cancer vaccines, the lack of immunogenicity remains an issue. Adjuvants are required to enhance the immunogenicity of antigens and activate the immune response. However, only a few adjuvants with acceptable toxicity have sufficient potency for use in cancer vaccines, necessitating the discovery of potent adjuvants. The most well-known cationic polymer polyethyleneimine (PEI) acts as a carrier for delivering antigens, and as an immunoadjuvant for enhancing the innate and adaptive immunity. In this review, we have summarized PEI-based adjuvants and discussed how to improve and boost the immune response to vaccines. We further focused on PEI-based adjuvants in cancer vaccines. Finally, we have proposed the potential challenges and future issues of PEI-based adjuvants to elicit the effectiveness of cancer vaccines.