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BACKGROUND AND OBJECTIVE: Our understanding of the effects of ionizing radiation on cells and cellular responses to radiation could result in the more effective use of radiation to treat cancer and reduce further complications of radiation therapy more efficiently. In this review article, the effects of ionizing radiation used in radiation on cells and biochemical pathways induced by radiation are discussed with emphasis on its clinical significance. METHODS: In a review article, the biological effects of ionizing radiation and their clinical importance were searched in databases of NCBI, Scopus and Magiran using key words such as ionizing radiation, biological effect, response to radiotherapy and microRNAs . The resulting papers were used in studying the biological effects of ionizing radiation, the reaction of patients to radiation and microRNAs. FINDINGS: The most significant component damaged in the ionizing radiation treatment of cells is DNA. The ability of cancer cells to repair DNA damage is very low. Thus, DNA lesions are not usually repaired and are transmitted to the next generation. The accumulation of mutations might lead to of the reduction of cell division or death of the cancer cell. In addition, ionizing radiation damages biological membranes. The phase of the cell cycle in which the cell is essentially affects its sensitivity to ionizing radiation. Finally, in response to radiation, different biochemical pathways are activated in the cells. CONCLUSION: By understanding the biochemical pathways involved in the response to ionizing radiation, the markers of sensitivity to radiotherapy could be determined. These markers are important for the appropriate use in radiotherapy and achieving success in treatment. They could also be used to increase the sensitivity of cancer cells to ionizing radiation and reduce the sensitivity of normal cells. Using these markers will enable us to increase the efficiency of radiotherapy and reduce damage to healthy tissues to a minimum.