Abstract: Objective To explore the mechanism of cisplatin-resistance of lung adenocarcinoma by evaluating the differences of GSK-3β and β-catenin expression localization in lung adenocarcinoma cell line A549 and its cisplatin resistance cell line A549/DDP. Methods MTT assay was used to determine IC₅₀ values of cisplatin in A549 and A549/DDP cells. Immunofluorescence method was used to detect GSK-3β and β-catenin expression localization. Results IC₅₀ value of cisplatin in A549/DDP cells was (28.984±1.404) μmol/L, higher than (5.888±0.338)μmol/L in A549 cells(t=27.696, P<0.001). GSK-3β expression localization in A549/DDP cell was mainly in the cytoplasm, while cisplatin changed its location to cytoplasm and nucleus. β-Catenin expression localization in A549/DDP cell was mainly in the membrance and cytoplasm, while cisplatin changed its location from cytoplasm to nuclear. However, GSK-3β and β-catenin expression localization in A549 cells had no change. Conclusion The mechanism of cisplatin-resistance of lung adenocarcinoma may be related to co-location of GSK-3β in cytoplasm and nucleus, and β-catenin location from cytoplasm to nuclear.