Abstract: Objective To declare whether BPA (Bisphenol A) induces the expression of LRP (lung resistance protein) and MDR (multi-drug resistance) process in vitro. Methods Series concentration gradient of BPA was used in dose-effect experiments inducing LRP expression. Then, ELISA assay was used to identify the effect of BPA on LRP and the EC₅₀ value (50% effective concentration) was calculated. The inhibition rate of anti-tumor drugs on A549 or A549/ADR was calculated by A_490nm from MTT assays and IC₅₀ values (50% inhibitory concentration) were calculated. Protein level of LRP induced by BPA with EC₅₀ concentration and the expression of LRP in A549/ADR were detected by western blot analysis. The small interfering RNA (siRNA) of LRP was transfected into A549/ADR cells to downregulate protein level of LRP, and its effect on MDR was investigated. Results Results from ELISA showed that BPA induced the expression of LRP in a dose-dependent manner (EC₅₀=0.55±0.12 μmol/L, R²=0.96, P=0.001 1), and BPA (EC₅₀ concentration) could downregulate the effects of Paclitaxel, Gemcitabine and Gefitinib to A549 with significant increase of IC₅₀ value(0.08±0.01) μmol/L vs (0.67±0.11) μmol/L, P< 0.05; (0.45±0.05) μmol/L vs (2.75±0.33) μmol/L, P< 0.05; (1.36±0.22) μmol/L vs (5.82±0.41) μmol/L, P< 0.05 and drug resistance of 7.12, 6.11, 4.28 times. In addition, Western blot analysis showed that high level of LRP was detected in A549/ADR cells compared with A549 cells. Transfection of LRP siRNA downregulated LRP expression and enhanced the sensitivity of A549/ADR cells to Paclitaxel(0.59±0.07) μmol/L vs (0.15±0.06) μmol/L, P< 0.05, Gemcitabine(3.95±0.66) μmol/L vs (0.86±0.14) μmol/L, P< 0.05 or Gefitinib(8.72±0.71) μmol/L vs (1.99±0.54) μmol/L, P< 0.05. Conclusion BPA can induce the expression of LRP and will participate in the MDR process in human lung cancer cells.