Eczema is a common skin disease associated with inflammation. Interleukin (IL)-24 is crucial in the pathogenesis of inflammatory diseases like eczema. The study objective was the assessment of IL-24 serum levels and its gene polymorphisms in eczematic Iraqi patients. This retrospective case-control study involved 145 participants, divided into 82 patients with eczema and 63 healthy controls. An enzyme-linked immunosorbent assay measured serum IL-24, while polymerase chain reaction and Sanger DNA sequencing were used for genotype analysis. Serum IL-24 level was significantly higher (P value < .001) in patients compared to controls (41.6 [interquartile range (IQR): 28.9–53.6] vs 9.8 [IQR: 0.8–19.6] pg/mL, respectively). DNA sequence illustrated 2 SNPs with polymorphic frequencies (rs1150256 G/A and rs3093425 del/ins). The first SNP (rs1150256 G/A) showed 3 genotypes (GG, AA, and G/A), while the second SNP (rs3093425) showed 3 genotypes (-/G del/Ins, G Ins/Ins, and - del/del). The subsequent investigation revealed the presence of the following findings within the DNA sequence of the PCR amplified region (329bp). In the control group, all participants had GG/G (wild type) genotype/allele for the rs1150256 SNP, while in eczematic patients, 24.4% GG, 50% GA, and 25.6% AA. For the second SNP genotype (rs3093425 del/ins), the genotype frequencies in patients vs control were (24.4% vs 84.1%, 50.0% vs 11.1%, and 25.6% vs 4.8; Del/Del, Del/Ins, and Ins/Ins, respectively). The presence of Ins compared to Del increased the risk of eczema by 8.91 (4.66–17.03); OR (95% CI). In conclusion, IL-24 is a good predictor of eczema and A-allele carrier for rs1150256 SNP, and insertion-allele carrier for rs3093425 SNP is associated with elevated serum IL-24 and higher risk of eczema.