Infection with human immunodeficiency virus (HIV) compromises the body's immune system leaving infected individuals vulnerable to other pathologies including cancer. Some forms of cancer typically develop in AIDS patients, as for example the very aggressive and most often deadly primary effusion lymphoma (PEL). There is currently no standard treatment for PEL but the use of anti-HIV drugs is associated with better prognosis. Here we show in preclinical tests that inhibitors of nuclear export suppress both HIV replication as well as PEL progression. These findings provide a rationale for further evaluating these inhibitors as treatment strategy for dual HIV/lymphoma therapy.