In this study, we identified 32 unique cytokines/chemokines that distinguish the HL proteomic profile from controls, as well as specific cytokines/chemokines associated with extent of disease (IL-8, IL-10, IFN-γ, TNF-α), therapy response (CCL13, IFN-λ1, and IL-8), and relapse/EFS (TNFSF10). Here, IFNL1 is linked to Hodgkins lymphoma.