OBJECTIVES: To investigate the influence of genetic variants IL-6 (-174 G/C) and interferon-gamma (IFNγ) (+ 874 A/T) on beta-globin gene expression, inflammation markers such as C-reactive protein (CRP), and their diagnostic impact on anemic Sudanese children with kidney failure. RESULTS: Severe and moderate anemia were observed in 88.9% of children aged 5-15 years. Semi-quantified molecular analysis of allele-specific genomic content (Lane%) revealed a correlation with disease severity. For interferon-gamma (+ 874 A/T), the AA genotype expressed the highest beta-globin gene Lane% value (5.22 ± 2.15), with beta-globin gene expression showing diagnostic utility at an area under the curve (AUC) of 0.646 (95% confidence interval (CI): 0.472-0.820). For IL-6 (-174 G/C), the CC genotype exhibited the highest Lane% value (5.82 ± 2.34), and Lane% content was more diagnostic compared to beta-globin gene expression, with an AUC of 0.715 (95% CI: 0.471-0.959). C-reactive protein showed significant diagnostic value as a marker of inflammation, with AUC values for interferon-gamma at 0.618 (95% CI: 0.443-0.793) and IL-6 at 0.663 (95% CI: 0.502-0.823). These findings highlight the role of IL-6 and interferon-gamma genetic variants in the severity of anemia and their diagnostic potential in children with kidney failure.