Abstract: OBJECTIVE To analyze the association of apolipoprotein E (ApoE) and interleukin-8 (IL-8) gene polymorphisms with Mycoplasma pneumoniae pneumonia in children. METHODS The clinical data of 156 children with Mycoplasma pneumoniae pneumonia (MPP) (set as MPP group) between Aug. 2018 and Aug. 2021 in the First People' s Hospital of Chongqing Liangjiang New Area were retrospectively analyzed, and 156 children with healthy physical examination matched by gender and age at 1∶1 were included as control group. The distribution characteristics of genotypes and gene frequencies at rs7412 locus and rs429358 locus of ApoE gene and at rs4073 locus and rs2227306 locus of IL-8 gene were compared between the two groups. The relationship between ApoE and IL-8 gene polymorphisms and bronchial mucosal morphological changes and prognosis and outcomes in children with MPP was analyzed. RESULTS The Hardy-Weinberg equilibrium test suggested that the frequencies of each gene were consistent with the law of genetic equilibrium and had a good population representation. The frequencies of CC genotype and allele C at rs429358 locus of ApoE gene in MPP group were higher than those in control group (P<0.05). The relative risk OR of MPP in patients with CC genotype was 3.694, and the OR of MPP in patients carrying allele C was 1.849. The frequencies of AA genotype and allele A at rs4073 locus of IL-8 gene were higher in MPP group than those in control group (P<0.05), and the OR of MPP in patients carrying AA genotype was 4.104 and the OR of MPP in patients carrying allele A was 1.457. There were significant differences in bronchial mucosal morphology and prognostic outcome time of different genotypes at rs429358 locus of ApoE gene and at rs4073 locus of IL-8 gene (P<0.05). The type of CC genotype at rs429358 locus of ApoE gene and AA genotype at rs4073 locus of IL-8 gene with mucus plug obstruction were the most (P<0.05), and the fever abatement time, cough disappearance time, pulmonary rales disappearance time and hospital stay were longer (P<0.05). CONCLUSION The polymorphisms at rs429358 locus of ApoE gene and at rs4073 locus of IL-8 gene were associated with the MPP susceptibility, the morphology of bronchial mucosa and the prognosis and outcomes of children, which were expected to be new targets for the diagnosis and treatment of MPP.