Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for Alzheimer's disease and seems to be related to cognitive decline and damaged event-related potential P300, which is a sensitive measure to assess cognitive processing. This research aims to critically review the existing scientific evidence regarding the association between APOE4 and P300. A systematic review was carried out up to January 2020 on the following databases: Web of Science, Scopus and Medline/PubMed. Articles were considered for inclusion if they are original research that provided information regarding the association between APOE4 and P300, available in English, Spanish, or Portuguese, and available in full text. The methodological quality of the studies selected was evaluated using the quality assessment tool for observational cohort and cross-sectional studies recommended by Cochrane. Out of 993 studies, 14 met the inclusion criteria. The results obtained showed that APOE4 is related to a longer P300 latency. However, the data supplied do not allow us to confirm if this relationship also occurs in amplitude measures. Moreover, it was observed that APOE genotype may influence P300 in different ages, from younger individuals to demented older people. Evidence shows that APOE4 negatively influences cortical activities related to cognitive functions, as indicated by P300.