Natural killer (NK)/T cell lymphoma is a highly aggressive subtype of non-Hodgkin lymphoma. The prognosis of patients with natural killer T cell lymphoma (NKTCL) remains poor. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R NKTCL. CD30 expression has been reported to occur in about 40% of NK/T cell lymphoma. Brentuximab vedotin (BV), a monomethyl auristatin E conjugated CD30 antibody, targets CD30 to kill cancer cells. Therapeutic combination of BV and bendamustine has been shown to be highly effective in Hodgkin lymphoma. We investigated efficacy of BV in treating NKTCL as a single therapy, and in combination with bendamustine in vitro and in vivo. We determined CD30 expression levels in 6 NKTCL cell lines. The efficiency of lymphoma cell inhibition by BV correlates with CD30 expression. We also determined the efficacy of BV in combination with bendamustine and found synergistic effects with bendamustine in NKTCL. Combined BV and bendamustine treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic in vitro and in vivo. Brentuximab vedotin and bendamustine synergistically arrested cell cycle at the G2/M phase in NKTCL cell lines. The combination of BV and bendamustine was demonstrated to synergistically damage DNA in NKTCL. This study provides a reference for possible application on using BV for the treatment of NKTCL, either as a single agent or in combination with bendamustine.