A biodegradable alginate coated chitosan hollow nanosphere (ACHN) was prepared by a hard template method and used for codelivery of doxorubicin (DOX) and paclitaxel (PTX) to investigate the effect on human lung cancer A549 cells. PTX was loaded into the nanometer hollow structure of ACHN through adsorption method. DOX was coated on surface of ACHN through electrostatic interaction. Drug release studies exhibited a sustained-release effect. According to X-ray diffraction patterns (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) analysis, DOX structure in the loading samples (DOX-PTX-ACHN) was of amorphous state while PTX was microcrystalline. Cytotoxicity experiments showed ACHN was nontoxic as carrier material and the combination of DOX and PTX in DOX-PTX-ACHN exhibited a good inhibiting effect on cell proliferation. Cell uptake experiments demonstrated that DOX-PTX-ACHN accumulated in the cytoplasm. Degradation experiments illustrated that ACHN was a biodegradable material. In summary, these results clearly indicate that ACHN can be utilized as a potential biomaterial to transport multiple drugs to be used in combination therapy.