<p>Epiregulin, a polypeptide involved in inflammation, cell proliferation, tumor development, and tissue remodeling pathophysiology, plays a crucial role in the etiopathogenesis of malignancies. This prospective case-control study aimed to investigate the association between epiregulin levels and various clinical and laboratory parameters in HL patients to better understand its role in the disease. This study compared newly diagnosed 56 HL patients with 56 healthy controls to assess epiregulin levels in relation to factors such as cell type, staging, extranodal involvement, β2-microglobulin, lactate dehydrogenase (LDH), and C-reactive protein (CRP). Epiregulin levels were significantly elevated in HL patients (265.0 ± 36.0 pg/ml) compared to healthy controls (130.7 ± 21.8 pg/ml). While no significant differences were observed in epiregulin levels among different HL subtypes, higher levels were found in advanced stages (281.1 ± 32.2 pg/ml) compared to early stages (246.4 ± 31.3 pg/ml). Patients with splenic and extranodal involvement exhibited elevated epiregulin levels. Furthermore, a positive correlation was noted between epiregulin levels and CRP, LDH, and β2-microglobulin levels in HL patients. Epiregulin levels are elevated in patients with Hodgkin lymphoma and are associated with advanced disease stage, extranodal and splenic involvement, the presence of B symptoms, and key laboratory parameters. These findings suggest that epiregulin may be related to disease burden and activity in HL. Further prospective studies are warranted to clarify its clinical relevance.</p>