Objective To investigate the molecular mechanism of Buzhong Yiqi Decoction in coordination with Siβ-catenin in intervention against cisplatin resistance in A549/DDP cells by regulating the Wnt/β-catenin signaling pathway. Methods The expression of β-catenin was silenced by siRNA interference，and Western blot was used to measure the relative protein expression of β-catenin in A549/DDP cells in the normal serum group，the cisplatin group，the siCTNNB1-235 group，the siCTNNB1-510 group，and the siCTNNB1-547 group. After β-catenin interference，Western blot was used to measure the protein expression levels of β-catenin and Survivin in A549/DDP cells of each group； MTT assay was used to determine the IC₅₀ of cisplatin in A549/DDP cells of each group； Annexin V/PI staining was used to measure the cisplatin-induced apoptosis rate of A549/DDP cells in each group. Results Compared with the normal serum group（1.00），the siCTNBN1-235 group（0.323±0.021） had an inhibition rate of 67% on β-catenin expression（P=0.000）. After β-catenin was silenced by RNAi technique，compared with the normal serum group（1.00），the Buzhong Yiqi Decoction+cisplatin group had significantly greater reductions in the protein expression of Survivin（0.247±0.015） and β-catenin（0.257±0.015）（P=0.000，P=0.000）. As for the IC₅₀ of cisplatin in A549/DDP cells，compared with the normal serum group（28.330±1.029） μmol/L，serum containing Buzhong Yiqi decoction alone（20.350±1.155） μmol/L or siCTNNB1-235 transient transfection alone（15.577±1.535） μmol/L reduced the IC₅₀ of cisplatin in A549/DDP cells（P=0.000，P=0.000），and the combination of the two methods（10.453±0.999） μmol/L further reduced the IC₅₀ of cisplatin（P=0.000）. Compared with the normal serum group（9.130±0.384）%，the siCTNBN1-235 transient transfection+cisplatin group（64.393±0.244）% and the Buzhong Yiqi Decoction+cisplatin group（70.120±0.400）% had a significant increase in overall apoptosis rate（P=0.000，P=0.000）. Conclusion Serum containing Buzhong Yiqi Decoction and siβ-catenin transient transfection have a synergistic effect on inhibiting the Wnt/β-catenin signaling pathway and improving cisplatin resistance in lung adenocarcinoma，and Buzhong Yiqi Decoction has a siβ-catenin transient transfection-like effect.