To explore the effects and underlying mechanism of Curculiginis Rhizoma decoction and orcinol glucoside(OG)，the main plasma component，on cisplatin-resistant cells(A549/cis) in non-small cell lung cancer(NSCLC).Methods:The binding affinity of OG to P-glycoprotein(P-gp) was evaluated by AutoDock Vina.CCK-8 assay was used to detect the cell viability inhibition rate of cisplatin，Curculiginis Rhizoma decoction，OG，and their combination on A549/cis cells.The P-gp expression level in A549/cis cells was detected by Western blot.Results:The binding energy of simulated molecular docking of OG to P-gp was -7.6 kcal/mol(1 cal=4.184 J)，indicating that they had good binding activity.The half-maximal inhibitory concentration(IC50) of cisplatin on A549/cis cells was about 5.5 μg/mL.Curculiginis Rhizoma decoction or OG in the gradient concentrations showed no significant effect on the viability of A549/cis cells.The cell inhibition rates in drug combination groups［low-dose cisplatin(1.5 μg/mL) combined with high-and low-dose Curculiginis Rhizoma decoction(1 000 and 500 μg/mL) or high-dose OG(5×10-5 mol/L)，and medium-dose cisplatin(4 μg/mL) combined with high-and low-dose Curculiginis Rhizoma decoction(1 000 and 500 μg/mL) or high-and low-dose OG(5×10-5 and 1×10-5 mol/L)］ were higher than that in the cisplatin group(P<0.05 or P<0.01).The P-gp expression levels of A549/cis cells in groups of cisplatin(1.5 μg/mL) combined with Curculiginis Rhizoma decoction(1 000 μg/mL) or OG(5×10-5 mol/L) were both lower than that of the cisplatin group，and P-gp expression level in the group of cisplatin combined with Curculiginis Rhizoma decoction lowered significantly(P<0.05).Conclusion:Curculiginis Rhizoma decoction and OG can both reduce the drug resistance of A549/cis cells，and the sensitivity-enhancing mechanism may be related to the inhibition of P-gp expression.