Objective To evaluate the cytotoxic effect of photodynamic therapy (PDT) combined with targeted therapy using cross- linked liposomes and gels (Ce6-PC-Tmab@A-Gel) loaded with photosensitizer Chlorin (Ce6) and the tumor- targeting drug Trastuzumab (Tmab) in drug-resistant HER2+ breast cancer cells. Methods Ce6-PC-Tmab liposomes were prepared using the thin-film hydration method. The general properties, encapsulation efficiency and near-infrared responsivity of the nanoparticles were evaluated. Ce6-PC-Tmab@A-Gel with a shear response was prepared by freeze drying and stirring crosslinking, and its microstructure was observed with scanning electron microscopy (SEM) and the shear response evaluated using a rheometer. The inhibitory effect of Ce6-PC-Tmab@A-Gel in drug-resistant HER2 + breast cancer SK-BR-3 cells was assessed with cytotoxicity assay (MTT assay) combined with near-infrared light. Results The particle size of Ce6-PC-Tmab was 239.7±9.7 nm and the potential was -2.03±0.09 mV. The entrapment efficiency of Tmab by Ce6-PC-Tmab liposomes was (40.22±0.73)%. The prepared Ce6-PC-Tmab@A-Gel had a good shear response with excellent drug release characteristics under near-infrared light, and increased intensity and duration of near-infrared light exposure enhanced Tmab release from the gel. Ce6-PC-Tmab@A-Gel was stable at room temperature and in a simulated tumor microenvironment (pH 6.25). Cytotoxicity assay (MTT) showed that Ce6-PC-Tmab@A-Gel combined with near-infrared light resulted in a survival rate of (31.37±1.73)% in SK-BR-3 cells, much lower than that in the control group and other treatment groups (P<0.01); the combined treatment also had a high efficiency of ROS production, and ROS release reached (22.36 ± 0.11)% after 2 min of near-infrared light exposure. Conclusion The prepared Ce6-PC-Tmab@A-Gel has good near-infrared light response release characteristics to ensure effective targeted therapy with Tmab. The injectable gel system potentially allows long-term local drug release in the tumor to improve the treatment efficacy against drug-resistant breast cancer.