Objective To determine the association of high IL-1β levels with the migration of lung cancer H460 cells with acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods The resistant cells were referred to as H460-TR in this study. IL-1β levels in H460-TR cells and the parent H460 (H460-WT) cells were measured through RT-PCR, Western blot, and enzyme-linked immunosorbent assay. The migration capacity of the cells was determined using the migration transwell assay. The extent of migration and the activation of phosphatidyl-inositol 3-kinase/serine-threonine kinase (PI3K/Akt) were detected in H460 cells treated with or without human recombinant IL-1 or IL-1R antagonist. Results Migration capacity of H460-TR cells in the conditioned medium and its IL-1β level were higher than those of H460-WT cells . The migration capacity and Akt activation were consistent with the IL-1β level in lung cancer H460 cells. Conclusions Significantly elevated IL-1β expression in cancer cells is associated with the high migration capacity of H460-TR cells, and Akt activation. Akt signaling as the downstream pathway of IL-1β and IL-1βmay function as a therapeutic target for metastatic lung cancer.