Acute promyelocytic leukemia (APL) is mostly due to the chromosome translocation t (15; 17) (q22; q12), leading to the formation of PML-RARA fusion protein. Some patients carried rare translocation involving RARA gene, who were called variant APL caused by RAR family (RARA, RARB, and RARG) and partner genes. STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL. Knowledge of STAT5b-RARA (+) APL treatment is still limited. We presented a 38-year-old female variant APL case, who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction. The patient failed to respond after four-drug combined induction chemotherapy: idarubicin, cytarabine, all trans retinoic acid, and arsenic trioxide (As2O3). Then, the patient was re-induced with azacytidine, but still failed to achieve complete remission (CR). Next, she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR. Later, the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy. Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.