Background: Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against human lung cancer as well as potentiates the antitumor activity of cisplatin in A549 lung cancer xenograft model, if so, to examine the possible mechanism in the phenomenon. Methods: human A549 lung cancer-bearing nude mice were treated with liposomal honokiol, liposomal honokiol plus DDP or with control groups. Apoptotic cells and vessels were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31 respectively. Results: The present study showed that liposomal honokiol alone resulted in effective suppression of the tumor growth, and that the combined treatment with honokiol plus DDP had the enhanced inhibition of the tumor growth and resulted in a significant increase in life span. The more apparent apoptotic cells in the tumors treated with honokiol plus DDP was found in fluorescent in situ TUNEL assay, compared with the treatment with control groups. In addition, the combination of honokiol and DDP apparently reduced the number of vessels by immunolabeling of CD31 in the tissue sections, compared with control groups. Conclusion: In summary, our data suggest that honokiol alone had the antitumor activity against human lung cancer in A549 lung cancer xenograft model, and that the combination of honokiol with DDP can enhance the antitumor activity, and that the enhanced antitumor efficacy in vivo may in part result from the increased induction of the apoptosis and the enhanced inhibition of angiogenesis in the combined treatment. The present findings may be of importance to the further exploration of the potential application of the honokiol alone or the combined approach in the treatment of lung carcinoma.