<p indent="0mm">In this study, we designed and synthesized two novel porphyrin-modified graphdiyne derivatives (GDYO–TPP and GDY–TPP), which have good dispersity in organic solvents and water and exhibit favourable biocompatibility. It was found that the GDYO–TPP and GDY–TPP not only have excellent photothermal conversion performances, but also have outstanding singlet oxygen generation ability, and can be used for photothermal/photodynamic combination therapy of tumors, showing tremendous inhibition of tumor growth in animals, without side effects. Further studies showed that the efficient electron transfer between porphyrin and graphdiyne made the photothermal/photodynamic combination therapy effect of conjugated GDY–TPP much better than that of non-conjugated GDYO–TPP, which realized the regulation of the photothermal/photodynamic combination therapy by controlling the bonding mode of functional groups. The results provide new ways for designing novel functional graphdiyne and photothermal/photodynamic combination therapy of tumors.