Photodynamic therapy (PDT) is a non-invasive cancer therapy method that has been clinically approved for many years. Due to strong optical scattering and absorption of tissues, optical photons can only penetrate tissues several millimetres, which limits the applications of PDT to superficial lesions. To overcome the limitation of penetration depth, here we applied Cerenkov radiation, as generated by the high-energy -rays from radionuclide Cesium-137, to directly activate the porphyrin-based photosensitizer MPPa (Pyropheophorbide-a methyl ester) without any additional energy mediators. Experiments were conducted with A549 human lung carcinoma cell line. Moreover, to reduce the effects of possible plastic scintillation on PDT, we used black cell culture plates in these studies. We have also shown that the effects of the scintillations on PDT could be minimized. In our studies, we have excluded the effects of radiotherapy and drug toxicity. Our results indicated that the Cerenkov radiation generated from high energy -rays could be used to activate the photosensitizer MPPa in PDT, which could potentially overcome the penetration limitations of optical photon-based PDT, making the PDT a feasible and complementary cancer therapy for deep lesions.