Oncoprotein Bcl-3 is perceived as an unusual member of IκB family since it can both stimulate and suppressNF-κB activation. Aberrant Bcl-3 results in increased cell proliferation and survival, suggesting a contributionto malignant potential and elevated levels of Bcl-3 have been observed in many HTLV-1-infected T cell lines andATL cells. To investigate the specific roles of Bcl-3 in HTLV-1-infected cells, we knocked down Bcl-3 expressionusing shRNA and then examined the consequences with regard to DNA damage and cell proliferation, as wellas NF-κB activation. The HTLV-1 encoded protein Tax promotes Bcl-3 expression and nuclear translocation.In HTLV-1-infected cells, Bcl-3 knockdown obviously induced DNA damage. Cell growth and NF-κB activationwere reduced in HTLV-1-infected or Tax positive cells when Bcl-3 expression was decreased. Together, our resultsrevealed positive roles of Bcl-3 in DNA stabilization, growth and NF-κB activation in HTLV-1-infected cells.