Interleukin‑1β (IL‑1β) has a significant role in osteoarthritis (OA). The purinergic receptor, P2X4, has previously been implicated in IL‑1β secretion. The NLRP1 inflammasome mediates the production of IL‑1β in inflammatory disorders. However, it is unknown whether P2X4 modulates NLRP1‑mediated IL‑1β release. In the present study, the correlation between the P2X4 receptor and NLRP1 was investigated in OA fibroblast‑like synoviocytes (OAFLS). The expression of P2X4 and NLRP1 was detected in the OAFLS. The OAFLS were stimulated with P2X4 and the levels of IL‑1β and matrix metalloproteinases (MMPs) were measured. To determine whether P2X4 is involved in NLRP1‑triggered IL‑1β production, NLRP1 small interfering RNA (siRNA) was used. In the OAFLS, a markedly higher expression of P2X4 and NLRP1 was revealed compared with that in the normal FLS. OAFLS stimulated by P2X4 resulted in concentration‑dependent increases in the production of IL‑1β, MMP‑3 and MMP‑9. Furthermore, P2X4‑mediated IL‑1β production was attenuated by the NLRP1 siRNA. The results of the present study indicate that P2X4 induced IL‑1β, MMP‑3 and MMP‑9 production in the OAFLS. IL‑1β induced by P2X4 is mediated via NLRP1. P2X4/NLRP1 may be important in the pathogenesis of OA and may represent a novel therapeutic target.