The aim of this work was to evaluate the therapeutic potential of an NRF2 inhibitor, Brusatol (BRU), in monotherapy and in association with the BTK inhibitor Ibrutinib (IBR), in an in vitro CLL model, the HG-3 cell line….The results showed that HG-3 cells express NFE2L2 and KEAP-1 genes....BRU in monotherapy and in association with IBR induce a cytostatic and cytotoxic effect, mediated by cell cycle arrest in phase G0/G1 and apoptosis, respectively....Our results suggest that BRU could be a potential pharmacological agent for the therapeutic approach of CLL, in monotherapy and as an adjuvant to treatment with IBR.