OBJECTIVE: To prepare zedoary turmeric oil compound liposomes (ZTOC-LPS) and evaluate its quality. METHODS: The preparation method of liposome, the addition amount of soybean phosphatidylcholine (SPC), ratio of SPC to cholesterol (CH) in lipid, drug-lipid ratio of zedoary turmeric oil (ZTO), drug-lipid ratio of tretinoin in formulation, and water bath temperature were screened using encapsulation efficiency and drug-loading amount of ZTO (represented by germacrone) and tretinoin as investigation indexes. Quality evaluation and primary stability investigation were conducted for liposomes prepared by optimal preparation technology. RESULTS: The optimal preparation method was ethanol injection method; The optimal preparation technology were SPC 4 mg in 1 mL lipid, the mass ratio of SPC to CH 3 ∶ 1, the ratio of ZTO to lipid 1 ∶ 9 , the ratio of tretinoin to lipid 1 ∶ 70, water bath temperature of 55 ℃. Encapsulation efficiencies of ZTO and tretinoin were (64.63±1.00)% and (90.33±0.72)% in 3 batches of ZTOC-LPS, respectively. Drug-loading amount of ZTO and tretinoin were (9.09±0.14)% and (1.43±0.02)%, respectively. Particle size was (257.41±7.58) nm, Zeta potential was (-38.77±0.81) mV, PDI was 0.10±0.04; the results of centrifugal acceleration test showed that the liposomes had good physical stability. No obvious change was found in each investigation index of ZTOC-LPS that stored at (4±2) ℃ for 1 month. CONCLUSIONS: Established preparation technology is simple and feasible, the quality of the prepared ZTOC-LPS conforms to the requirements, and it can provide reference for the following research of ZTOC-LPS.