Objective To determine the reversal effect of psoralen on multidrug resistance (MDR) in the harringtonine (HT)-resistant leukemic cell line HL60/HT. Method The modulating effect of psoralen on MDR in HL60 and HL60/HT cells were determined by the measurement of cell growth and viability via MTT assay. High performance liquid chromatography(HPLC) was used to analyze intracellular HT concentrations in HL60/HT and HL60 cells treated with psoralen. Result Psoralen from 1 to 20 μmol/L could reduce the value of IC50 to HT and enhance the accumulation of HT in HL60/HT cells. Conclusion Psoralen can reverse MDR of HL60/HT cells and is a potential modulator of MDR.