The serum cytokines such as IL-10, CXCL-10 and IFNg are significantly elevated, yet there is limited knowledge regarding the association between serum cytokine methylation patterns and PB methylation status for these genes. Methods: This case control study included 50 newly diagnosed HL patients and 50 matched healthy controls from Iraq. Serum levels of IL-10, CXCL 10 and IFN γ were measured by ELISA, and methylation percentages of promoter regions of IL-10, CXCL-10 and IFNG were assessed by qMSP. Correlation analyses evaluated associations between cytokines and their methylation status, as well as inter gene methylation relationships. Results: CXCL 10 (423.2 vs. 14.7 pg/mL) and IFN γ (704.1 vs. 84.7 pg/mL) (all p<0.0001). Methylation of CXCL-10 (64.4% vs. 52.3%, p=0.040) and IFNG (90.2% vs. 27.0%, p<0.0001) was significantly higher in patients, while IL-10 methylation did not differ between groups (p=0.190). Strikingly, a robust positive correlation was observed between IL-10 methylation and CXCL-10 methylation (Pearson r = 0.545, p < 0.001) in HL patients. No significant correlations were found between any cytokine level and its own methylation percentage. EBV status (78% seropositive) did not influence either cytokine levels or methylation values. In conclusion, there is a clear positive relationship with both IL-10 and CXCL 10 methylation, indicating a potential linkage of dysfunction of epigenetics within HL regardless of the EBV status. The dissociation of hypermethylation from the cytokine overexpressed within HL suggests that the local specific environment takes precedence over repressive DNA methylation marks.