The usual prognostic scores used in cHL fail to identify some patients with worst outcome either in early or advanced stage HL. Pre-treatment cytokines, soluble receptor, cytokine signature (Casasnovas JCO 2007) and TARC profile have been described as biological markers correlated to tumour burden, to response and outcome. To evaluate the impact of TARC, IL6, IL1-RA, sCD30 and TNF-R1 levels on response and outcome, we collected plasma from 50 newly diagnosed cHL patients at baseline, during therapy and at the end of chemotherapy. We also analysed the correlation of usual prognostic factors with cytokines and soluble receptor level. Between April 2010 and November 2013, 50 cHL patients were enrolled (26 M/ 24F), median age was 31 years (18,5-63). Main clinical characteristics were as follow: stage I-II in 24 patients (according to EORTC classification: favourable: 7 and unfavourable: 17) and stage III-IV in 26 patients (IPS 1-2: in 15 patients). Thirty five patient were treated with ABVD and 15 patients with eBEACCOP. Radiotherapy was added in 24 patients. Mean TARC level was 281 pg/ml (27-83098), mean IL6 level was 2.9 pg/ml (0,6-175), mean IL1-RA was 252 pg/ml (0,9-6609), mean sCD30 level was 33 U/ml (8,8-1007), and mean TNR-F1 level was 2129,5 ng/ml (314-8463). Baseline cytokines level or cytokines signature did not correlate significantly with any clinical or biological factors nor with FDG-PET response. Ten patients disclosed relapse or progressive disease (R/R), only two patients died. With a median follow-up of 48 months, the event free survival (EFS) and overall survival (OS) at 3 years are 82% (95% CI 68-90) and 96% ( 95% CI 85-99) respectively. None of the classical prognostic factors as early response evaluated with FDG-PET were correlated with PFS. Neither baseline cytokines levels nor cytokine signature or early reduction of IL1-RA, sCD30, TNR-F1 level impacted significantly the outcome, but a trend was noted with early reduction of TARC and IL6. The decrease of TARC and IL6 seems to predict response to therapy and EFS. Unfortunately we failed to demonstrate any correlation between baseline cytokines or cytokine signature with biological or clinical characteristics, and outcome in this population. Surprisingly none of the usual prognostic factors predict outcome. These results could be perhaps explained by the small number of patients and should be confirmed in a larger prospective study.