This study reports the development of nanographene-porphyrin hybrids (NGP-1 and NGP-2) as a new class of near-infrared-II (NIR-II, 1000–1700 nm) responsive organic agents for photoacoustic imaging (PAI)-guided photothermal therapy (PTT) in cancer treatment. The π-extended porphyrins, fused with one or two nanographene units, exhibit absorption peaks in the NIR-I (≈1000 nm) and NIR-II (≈1400 nm) windows. These hybrids are encapsulated into self-assembled nanoparticles (NPs) for water dispersibility, achieving high photothermal conversion efficiencies of 60% and 69% under 808 nm and 1064 nm laser irradiation, respectively. NGP-2 NPs demonstrate promising photoacoustic responses, high photostability, and biocompatibility, enabling efficient PAI and NIR-II PTT in cancer cells both in vitro and in vivo. In vivo experiments using 4T1 tumor-bearing mice showed that NGP-2 NPs could accumulate in tumors, induce rapid tumor temperature升高, and effectively eliminate tumors without recurrence. The study highlights the potential of these nanographene-porphyrin hybrids for advanced cancer phototheranostics and other bioapplications.This study reports the development of nanographene-porphyrin hybrids (NGP-1 and NGP-2) as a new class of near-infrared-II (NIR-II, 1000–1700 nm) responsive organic agents for photoacoustic imaging (PAI)-guided photothermal therapy (PTT) in cancer treatment. The π-extended porphyrins, fused with one or two nanographene units, exhibit absorption peaks in the NIR-I (≈1000 nm) and NIR-II (≈1400 nm) windows. These hybrids are encapsulated into self-assembled nanoparticles (NPs) for water dispersibility, achieving high photothermal conversion efficiencies of 60% and 69% under 808 nm and 1064 nm laser irradiation, respectively. NGP-2 NPs demonstrate promising photoacoustic responses, high photostability, and biocompatibility, enabling efficient PAI and NIR-II PTT in cancer cells both in vitro and in vivo. In vivo experiments using 4T1 tumor-bearing mice showed that NGP-2 NPs could accumulate in tumors, induce rapid tumor temperature升高, and effectively eliminate tumors without recurrence. The study highlights the potential of these nanographene-porphyrin hybrids for advanced cancer phototheranostics and other bioapplications.