The present study aimed to determine the underlying mechanism of toll‑like receptor (TLR) agonist polyinosinic:polycytidylic acid (Poly I:C)‑induced apoptosis in THP‑1 cells following silencing the expression of tumor necrosis factor α‑induced protein 8‑like 2 (TIPE2). THP‑1 cells were incubated with different concentrations of the TLR agonist. Following incubation, reverse transcription‑quantitative polymerase chain reaction was performed to quantify the mRNA expression of TIPE2. Lentiviral technology was used to silence the expression of TIPE2. MTT assay was performed to assess cell proliferation, Annexin V/PI double staining was used to evaluate the apoptosis and western blotting was used to determine the expression levels of caspase‑8 following TIPE2 silencing. The TLRs agonist Poly I:C increased the expression level of TIPE2. During the incubation, Poly I:C also inhibited the proliferation of THP‑1 cells and induced apoptosis. Following silencing of TIPE2 in THP‑1 cells, the Poly I:C‑induced TIPE2 expression was significantly downregulated. Additionally, the Poly I:C‑induced proliferation inhibition and apoptosis in THP‑1 cells were significantly reduced following silencing of TIPE2. The findings of the western blot analysis indicated that the active form of caspase‑8, p18, was downregulated following silencing of TIPE2. In conclusion, the expression of TIPE2 in THP‑1 cells may be upregulated by Poly I:C, which may also inhibit cell proliferation and induce apoptosis. Following the downregulation of TIPE2 the aforementioned effect of Poly I:C treatment was reversed and may be associated with the reduced activity of caspase‑8 that was observed in the TIPE2 silenced group.