Background: Interleukin-17 (IL-17) gene polymorphisms have been implicated in modulating immune responses and inflammation, which are critical factors in leukemia pathogenesis. Objective: This study aimed to investigate the association between the IL-17 rs3819024 polymorphism and physiological markers—IRF8 and TGF-β—in leukemia patients compared to healthy controls. Methods: A total of 90 participants aged 16 to 45 years were enrolled, including leukemia patients and healthy controls. Genotyping of IL-17 rs3819024 was performed using the Tetra-ARMS PCR technique. Serum levels of IRF8 and TGF-β were measured by ELISA. Statistical analyses assessed differences in marker levels between genotypes and groups, alongside allele and genotype frequency comparisons. Results: The AG genotype carriers among leukemia patients displayed slightly elevated IRF8 (42.24 ng/mL) and TGF-β (45.66 ng/mL) mean levels but the confidence intervals overlapped. The AA genotype carriers among healthy controls showed elevated IRF8 levels but AG carriers displayed significantly higher TGF-β levels (32.88 ng/mL vs. 15.29 ng/mL). The G allele and AG genotype appeared more frequently in healthy controls than in leukemia patients according to allelic analysis which indicated a protective effect against leukemia. The correlation between IRF8 and TGF-β showed weak results that failed to reach statistical significance. Conclusion: The IL-17 rs3819024 polymorphism produces different effects on IRF8 and TGF-β expression between leukemia patients and healthy individuals which could influence their immune regulation and disease susceptibility. Further research is needed to understand the role of IL-17 in leukemia pathophysiology based on these findings.