Objective To investigate the distribution of different apolipoprotein E (ApoE) genotypes in hyperlipidemia patients living in central and southern Jiangsu province so as to provide evidence and reference for clinical use of statins in these patients. Methods A retrospective study was conducted on 676 hyperlipidemia patients admitted in Northern Jiangsu People′s Hospital and the First Affiliated Hospital of Soochow University from August 2019 to January 2022. Polymorphisms of ApoE 388T>C (rs429358) and 526C>T (rs7412) were detected, and the patients were divided into three groups according to genotyping:ApoE2, ApoE3 and ApoE4 groups. The relevant medical records of the patients were collected and retrospectively analyzed, and the distribution of ApoE polymorphisms and genotypes were also analyzed in the whole population and between different genders. SPSS statistics 26.0 was used for data analysis. Analysis of variance or Chi-square test was employed for intergroup comparison depending on data type. Results For the three groups of hyperlipidemia patients, there were six ApoE gene phenotypes detected in this study, sequentially as E3/E3 (458 cases, 67.75%), E3/E4 (109 cases, 16.12%), E2/E3 (86 cases, 12.72%), E4/E4 (11 cases, 1.63%), E2/E4 (10 cases, 1.48%) and E2/E2 (2 cases, 0.30%). The observed value of ApoE gene mutation was consistent with Hardy-Weinberg genetic equilibrium (P>0.05), and all the participants were from the same Mendelian inheritance. No significant difference was found in the distribution of ApoE genotypes between males and females (P>0.05). Conclusion The distribution of ApoE gene in central and southern Jiangsu province is not uniform, and there is no difference between genders. The characteristics of ApoE gene polymorphisms have reference value for precise lipid-lowering therapy in clinical practice.