Background: Acute myeloid leukemia (AML) is highly heterogeneous, and more than half of patients (pts) will experience refractory or relapse, with poor prognosis. Currently, chemotherapy and hematopoietic stem cell transplantation (HSCT) are the main treatments for AML. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics and significantly prolong the survival time of animals compared with the same dose of mitoxantrone (Li 2008). However, there is still a lack of systematic reports about the real-world application of PLM60 in AML. Methods: We performed a multicenter retrospective analysis of 82 pts with newly diagnosed AML and relapsed/refractory (R/R) AML, who received at least one cycle of PLM60 regimen between January 2022 and November 2022. Pts aged 18 years and above with confirmed diagnosis of AML according to the 2016-revised WHO criteria were eligible for inclusion, except acute promyelocytic leukemia (APL). The median dose of PLM60 in the regimen was 20.0 (range 10.3–31.6) mg/m². Efficacy was assessed by composite complete remission (CRc) rate and overall response rate (ORR), and logistic regression analysis was performed to analyze factors affecting the curative effect. Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: 82 pts were enrolled with a median age of 50.5 (range 20-83) years. There were 71 cases of de novo AML and 11 cases of secondary AML. Targeted sequencing was performed on 86.6% of pts (71/82). FLT3 was the most commonly mutated gene found in 22.5% (16/71), followed by ASXL1 mutated in 12.7%, NPM1 in 11.3%, and TP53 in 11.3%. 4.9% (4/82) of pts underwent HSCT. Among the 25 newly diagnosed pts, CRc rate was 72.0% (18/25) and ORR was 92.0% (23/25). Among the 57 R/R pts, CRc rate was 24.6% (14/57) and ORR was 40.4% (23/57). The courses of induction failure (OR= 16.617, P= 0.026), and the duration of the first complete remission (CR1) (OR= 20.647, P= 0.007) were independent influencing factors of the efficacy. Common grade 3/4 AEs included decreased neutrophil count (84.1%), thrombocytopenia (76.8%), anemia (73.2%), febrile neutropenia (47.6%), pulmonary infection (11.0%) and upper respiratory tract infection (2.4%). The overall safety was acceptable and controllable. Conclusions: The PLM60 regimen had an encouraging efficacy and showed a manageable safety profile with the most adverse events being hematologic toxicities.