The non-selectivity and undesirable water solubility are major limitations for the utilization of anti-cancer drugs in traditional therapy, leading to diminished therapeutic efficacy and severe side effects. Besides, the tumor inhibitory effect of photodynamic therapy (PDT) is limited, due to the limited depth of light penetration. However, combination therapies can reverse the dilemma that monotherapies face in clinical use. Here, a stimulus-sensitive drug delivery system was prepared by self-assembly for synchronized delivery and combination therapy. It was constructed by employing pH-responsive imine bonds to attach the chemotherapeutic drug daunorubicin (DNR) and the photosensitizer methyl aminolevulinate (MAL) to oxidized hyaluronic acid (OHA), named NPs(MAL/DNR). The nanoparticles demonstrated excellent inhibitory effect and synergistic effect in tumor suppression, as evidenced by in vitro cytotoxicity results (CI = 0.90, synergism). In summary, the prepared dual-drug nanoparticles can play a synergistic role in selectively killing tumor cells. This provides a new feasible direction for the use of combined chemotherapy and photodynamic therapy in the treatment of breast cancer.