In this study, a facile strategy for efficient codelivery of gene and drug was developed. Using a coprecipitation method, doxorubicin hydrochloride (DOX), an antitumor drug, and p53 expression plasmid were encapsulated in alginate/CaCO3/DNA/DOX nanoparticles with high encapsulation efficiency. The in vitro cell inhibition effect of the alginate/CaCO3/DNA/DOX nanoparticles was evaluated by MTT assay in HeLa cells. The alginate/CaCO3/DNA/DOX nanoparticles exhibited a high cell inhibition rate about 80%, indicating that the alginate/CaCO3/DNA/DOX nanoparticles could effectively mediate gene transfection and deliver the drug to the cells. Compared with the codelivery of gene and drug, the treatments by alginate/CaCO3/DOX nanoparticles and alginate/CaCO3/DNA nanoparticles separately led to much lower cell inhibition rates. Compared with the CaCO3/DNA/DOX nanoparticles without alginate modification, the alginate/CaCO3/DNA/DOX nanoparticles with a decreased particle size exhibited enhanced delivery efficiency. The alginate/CaCO3/DNA/DOX nanoparticles have promising applications in cancer treatments.