Cell division cycle 25A (CDC25A) is a core regulator of the cell cycle that has a dual‑specific phosphatase activity, which is closely associated with the occurrence and development of a tumor, and is overexpressed in liver cancer. However, the molecular mechanism of CDC25A in the development of liver cancer remains unclear. The purpose of the present study was to further investigate the effect of CDC25A on cell proliferation in vitro and in vivo and to investigate whether an interaction exists between CDC25A and interleukin (IL)‑6 in liver cancer. An Affymetrix human gene expression profiling chip screened differentially expressed genes in HepG2 cells with silenced CDC25A and the IL‑6 signaling pathway was revealed to be significantly inhibited (P<0.05). In the present study, the effects of CDC25A on cell proliferation and migration were analyzed using cell cycle, MTT and Transwell assays. Reverse transcription‑quantitative PCR, western blot and immunohistochemistry analyses confirmed that silencing the CDC25A gene downregulated the expression of IL‑6 in HepG2 cells and the mRNA and protein expression of IL‑1β, mitogen‑activated protein kinase kinase kinase 14 (NIK) and nuclear factor‑κB (NF‑κB), which are regulatory molecules upstream of IL‑6. In addition, silencing CDC25A by short hairpin RNA inhibited the development of liver cancer xenograft tumor types in nude mice, and decreased the expression of IL‑1β, NIK, NF‑κB and IL‑6 in xenograft tumor types. In conclusion, silencing CDC25A significantly inhibited the proliferation of liver cancer cells in vitro and in vivo, potentially via an interaction with IL‑6 through the downregulation of the IL‑1β/NIK/NF‑κB signaling axis.