Intracerebral hemorrhage (ICH) poses significant disability and mortality risks and perihematomal edema (PHE) plays a crucial role in ICH prognosis. The ApoE-ε4 allele has been implicated in exacerbating PHE and influencing neurological recovery post-ICH, yet, this specific association has not been explored much. This study aimed to investigate the correlation between ApoE-ε4 allele, PHE, and clinical prognosis in patients with ICH. We conducted a prospective observational cohort study at the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2023. We enrolled patients with supratentorial ICH patients and analyzed ApoE gene alleles, clinical baseline data, blood biochemical indices, and imaging findings. We considered ApoE-ε4 carrier status as an exposure variable and compared PHE volumes between ApoE-ε3 (ε3/ε3) and ApoE-ε4 (ε2/ε4, ε3/ε4, ε4/ε4) carriers. We also compared clinical and imaging characteristics between the good prognosis group (modified Rankin score 0-3) and the poor prognosis group (modified Rankin score 4-6). Finally, we examined the association between ApoEε4 and PHE volume and poor prognosis at discharge. Among 153 patients, 63 (41%) carried ApoE-ε4. ApoE-ε4 carriers had significantly higher PHE volumes at 24 h and on days 5-7 compared to ApoE-ε3 carriers. The poor prognosis group had a higher proportion of ApoE-ε4 carriers (53.9% vs. 28.6%, p = 0.001) and increased PHE volumes. ApoE-ε4 (OR 2.438, p = 0.02) and PHE (OR 1.048, p = 0.015) were independent predictors of poor prognosis. The area under the curve for ApoE-ε4 was 0.627, and for PHE volume, it was 0.698. The ICH patients carrying the ApoE-ε4 allele show severe PHE and poorer outcomes. Carrying ApoE-ε4 gene is an independent predictor for poor outcomes in patients with ICH.Trial registration: ClinicalTrials.gov, NCT05687201. Registered June 1, 2023, Effect of Apolipoprotein E on the Prognosis of Patients with Intracerebral Hemorrhage-Full Text View-ClinicalTrials.gov "prospective registered".