Various external lights and improved illumination methods, such as near-infrared light, X-ray, and two-photon excitation, have been tried to enhance the efficiency of photodynamic therapy (PDT) in deep-seated tumors. However, the penetration depth of light required for photosensitizers' (PSs) activation still remains a major problem in clinic. Herein, bioluminescence (BLS), a kind of inner light induced from the firefly luciferase, is attempted to activate the treatment in deep lesions. To obtain a better therapeutic effect, carbon dots (CDs) with an excitation-independent photoluminescence are prepared by a facile hydrothermal method, and the as-prepared CDs are designed to conjugate protoporphyrin IX (PIX) to construct the PDT agents (CDs-PIX). Results indicate the nano-carrier of CDs enhances the limitations of PIX and bridges the excitation between BLS and PIX. The BLS-induced PDT system can produce the singlet oxygen and provide a certain efficient therapy (about 60%) in SMMC-7721 hepatocellular carcinoma cells through fluorescence resonance energy transfer (FRET) process, which demonstrates the firefly BLS has already functioned in some extent, but not perfect. CDs-PIX is an excellent PS for PDT applications, but its corresponding excitation inner light source needs further studies.