This study introduces a novel molecular targeted cancer therapy, photoimmunotherapy (PIT), using a target-specific photosensitizer, IR700, conjugated to monoclonal antibodies (MAb) targeting epidermal growth factor receptors (EGFR). The MAb-IR700 conjugates were designed to be activated by near infrared (NIR) light, inducing cell death only when bound to the target cells. In vitro, the conjugates demonstrated strong association and no detectable aggregates, with high immunoreactivity. The conjugates induced rapid necrotic cell death upon NIR light irradiation, specifically in target cells expressing EGFR. The phototoxicity was target-specific, as shown by the lack of effect on HER2-negative cells. In vivo, the conjugates accumulated preferentially in HER1-positive A431 tumors, leading to significant tumor shrinkage and improved survival in treated mice. The study highlights the potential of PIT as a minimally invasive and highly selective cancer therapy, with the added benefit of real-time monitoring through the fluorescence of the conjugates.This study introduces a novel molecular targeted cancer therapy, photoimmunotherapy (PIT), using a target-specific photosensitizer, IR700, conjugated to monoclonal antibodies (MAb) targeting epidermal growth factor receptors (EGFR). The MAb-IR700 conjugates were designed to be activated by near infrared (NIR) light, inducing cell death only when bound to the target cells. In vitro, the conjugates demonstrated strong association and no detectable aggregates, with high immunoreactivity. The conjugates induced rapid necrotic cell death upon NIR light irradiation, specifically in target cells expressing EGFR. The phototoxicity was target-specific, as shown by the lack of effect on HER2-negative cells. In vivo, the conjugates accumulated preferentially in HER1-positive A431 tumors, leading to significant tumor shrinkage and improved survival in treated mice. The study highlights the potential of PIT as a minimally invasive and highly selective cancer therapy, with the added benefit of real-time monitoring through the fluorescence of the conjugates.