In this study, we found that ALKBH5, TIRAP and its downstream IRAK1 and TRAF6 were highly expressed in liver tissues of HCC patients with poor response to tumour radiotherapy and concomitant RILI, and functional experiments confirmed that the activation of TIRAP/NF‐κB pathway mediated by ALKBH5 significantly promoted RILF and decreased the radiosensitivity of HCC. The gene discussed is ALKBH5; the disease is neoplasm.