RespiratoryStaphylococcus aureusinfection represents a common complication in lung cancer patients, which is characterized with progressively and recurrently intratumor invasion. Although bacteriophages are widely reported as an effective bioweapon for managing bacterial infections, its applicability in handling infectious complications during cancer chemotherapy remains unknown. In this work, we hypothesized cancer chemotherapeutics would influence the efficacy of bacteriophages. To verify this end, interactions between four anticancer drugs (Gemcitabine, Doxorubicin, Cisplatin, and Irinotecan) with phage K were investigated, where Cisplatin directly reduced phage titers while Gemcitabine and Doxorubicin partially inhibited its propagation. The antibacterial efficacy of drug-phage K combinations was tested in aS. aureusinfected cancer cell model. Doxorubicin enhanced the antibacterial capacity of phage K, destroying 22-folds of cell-associated bacteria than that of phage K alone use. Also,S. aureusmigration was remarkably reduced by Doxorubicin. Overall, our data suggested that Doxorubicin had synergistic effects with phage K in combatingS. aureusintracellular infection and migration. This work may broaden the options of indication for phage clinical transformation and also provide reference for the adjunctive application of chemo drugs in intracellular infection management.