Although there is a high curability rate with rituximab chemotherapy, approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) develop disease relapse or primary-refractory lymphoma. The prognosis of HIV+ DLBCL patients is even worse with limited therapeutic options. The case is presented of a 28-year-old man who was diagnosed with HIV-DLBCL, refractory to rituximab-based chemo-immunotherapies and radiotherapy before and maintained a pathologically complete regression with the infusion of haplotype-matched invariant NK T cells and anti-CD20 antibody. His abdominal mass kept shrinking during the period of follow-up without relapse to date. A combination of haplotype-matched invariant NK T cells was likely to reinvigorate the efficacy of anti-CD20 antibody and may offer a viable treatment option for refractory DLBCL patients.