Objective To explore the effect of high‑mobility group box 1 (HMGB1) on the activation of nucleotide‑binding oligomerization domain‑like receptor protein 3 (NLRP3) inflammasome in respiratory syncytial virus (RSV) infected THP‑1 monocytes. Methods THP‑1 cell line was routinely cultured for infection with RSV virus. The cultured THP‑1 monocytes were divided into four groups: a non‑RSV infection group, a RSV infection group, a RSV infection plus rHMGB1 group, and a RSV infection plus glycyrrhizin group. After RSV infection for 6 h, the cells were cultured for another 48 h. Then, their total proteins were extracted. The levels of NLRP3, apoptosis‑associated speck‑like protein containing CARD (ASC), cysteine aspartate specific protease (caspase‑1), and IL‑1β were detected by Western blot. Results The RSV infection group showed significantly higher levels of NLRP3, ASC, caspase‑1, and IL‑1β than the non‑RSV infection group (P<0.05). The levels of NLRP3, ASC, caspase‑1 and IL‑1β in the RSV infection plus rHMGB1 group were significantly higher than those in the RSV infection group (P<0.05). The levels of NLRP3, ASC, caspase‑1 and IL‑1β in the RSV infection plus glycyrrhizin group were remarkably reduced, compared with those in the RSV infection plus rHMGB1 group (P<0.05). Conclusion HMGB1 can cause inflammation through promoting the activation of NLRP3 inflammasome and then inducing the expression of IL‑1β in RSV infected THP‑1 monocytes.