The present study was designed to investigate the effects of high‑mobility group box 1 (HMGB1) knockdown on the proliferation, migration and invasion of the HONE‑1 human nasopharyngeal carcinoma cell line and explore the possible underlying mechanisms. HMGB1-knockdown HONE‑1 cells were generated by lentiviral transfection, and HMGB1 expression was demonstrated to be obviously decreased in these cells. A Cell Counting kit‑8 assay was used to determine cell proliferation, while flow cytometric analysis was employed to determine the apoptotic rate. In addition, in vitro wound healing, cell adhesion and invasion assays were performed to evaluate the metastatic potential of the cells. Western blot analysis was used to determine the protein expression of apoptosis signaling proteins caspase‑3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, receptor for advanced glycation end products (RAGE) as well as phosphorylated and total extracellular signal-regulated kinase 1/2 in HONE‑1 cells. The results of the present study demonstrated that HMGB1 knockdown suppressed the proliferation, migration and invasion of HONE‑1 cells, the mechanisms of which may be associated with the induction of mitochondria‑mediated apoptosis and inhibition of HMGB1/RAGE pathways.