Radiotherapy represents an effective curative strategy that along with surgery and chemotherapy is traditionally used in cancer treatment. An optimal therapy delivers accurate radiation doses to tumour while protecting surrounding normal tissue. Although radiotherapy regimens have improved in recent years, tumour radioresistance and normal tissue toxicity remain major challenges that considerably contribute to the effectiveness of cancer therapy. These factors affect especially radiosensitive individuals in the treatment of whom the balance between effective tumour killing and adverse normal tissue late effects turns out to be problematic. Understanding molecular mechanisms involved in tumour and normal tissue response is essential in order to improve radiotherapy outcome in the field of personalised medicine. Alteration in the global proteome of cells and tissues truthfully reflects the changes in physiology and pathophysiology of biological samples. This makes proteomics analysis a powerful tool principally enabling identification of radioresistance biomarkers in cancer and sensitivity biomarkers in individuals. Yet, the use of proteomics in cancer therapy is still in its infancy and more research is needed to fulfil the great promise of this technique. The present review summarises recent proteomic-based studies searching for biomarkers for more accurate prediction of radiotherapeutic response in tumour and normal tissue.