The effects of proliferative, apoptotic and anti‐proliferative stimuli on interferon regulatory factor 4 (IRF4) expression by Reed‐Sternberg (RS) cells were analysed using a panel of Hodgkin lymphoma (HL)‐derived cell lines. IRF4 expressed by HL cells was consistently upregulated after CD40 engagement; IRF4 was downregulated by agonistic anti‐CD95 antibodies in the FAS‐sensitive HDLM‐2 cells and after treatment with Adriamycin and Dacarbazine, two chemotherapic agents commonly used for HL treatment. These results demonstrated, for the first time, that IRF4 was up‐modulated by CD40 engagement, and down‐modulated by apoptotic and anti‐proliferative signals, suggesting an involvement of IRF4 also in HL pathobiology.