Aims: To overcome the resistance of lung cancer to paclitaxel. Methods: P-glycoprotein antibody-conjugated paclitaxel PEG-coated immunoliposomes (Pab-PTX-L) were prepared, and a series of quality evaluations, in vitro cell evaluation and assessment of their in vivo antitumor effect in mice were conducted. Results: The results showed that Pab-PTX-L was nano-sized with high encapsulation efficiency of paclitaxel. For the paclitaxel-resistant lung cancer A549/T cells, the cellular uptake and cell viability inhibition and apoptosis of Pab-PTX-L-treated cells were higher than those of the control groups. More importantly, Pab-PTX-L showed a good targeting and antitumor effect on tumor tissue in mouse experiments. Conclusion: This study will provide a new insight on enhanced paclitaxel delivery into paclitaxel-resistant cancer cells.