Introduction <p>Multiple myeloma is a malignant plasma cell proliferative disease that is still incurable. Individualized targeted precision therapy is the key to prolonging survival. Patients with multiple myeloma are highly heterogeneous, and patients with high-risk factors have a short median survival and poor prognosis. T(11;14) is the most common immunoglobulin heavy-chain translocation in multiple myeloma. Although it is still classified as a standard prognostic risk stratification factor based on cytogenetics, such patients have special cell biological behaviors, and the efficacy and prognosis of some patients with high-risk cytogenetics are worse than those of other standard-risk patients. Venetoclax is a highly selective oral BCL-2 inhibitor that shows good antitumor activity in relapsed and refractory multiple myeloma with t(11;14).</p> Case <p>A 71-year-old Asian female was diagnosed with relapsed and refractory multiple myeloma combined with t(11; 14); she was treated with VenDd (venetoclax + daratumumab + dexamethasone) after first-line treatment progressed. The patient achieved stringent complete response efficacy during second-line treatment, and bone marrow flow cytometry minimal residual disease continued to turn negative (10^–5 level), with a progression-free survival of 40&#xa0;months.</p> Conclusion <p>Venetoclax combination regimen achieved excellent efficacy and safety in the treatment of relapsed/refractory multiple myeloma with t(11;14) in this case. The treatment of patients with relapsed and refractory multiple myeloma with t(11;14) by venetoclax still needs to be confirmed by more clinical studies.</p>