Icariin (ICA) has been used as a promising anti‑aging drug; however, its underlying molecular mechanism is yet to be elucidated. The present study aimed to determine the anti‑aging molecular mechanisms of ICA. D‑galactose (D‑gal) was used to generate a cell aging model. IMR‑90 human lung fibroblasts were pretreated with different concentrations of ICA (1, 2, 4, 8 and 16 µmol/l) for 6 h and subsequently incubated with D‑gal (200 mmol/l) at 37˚C for 72 h. Senescence of IMR‑90 cells was assessed by senescence‑associated‑β‑galactosidase (SA‑β‑Gal) staining assay. Cell viability, and the expression levels of p53/p21, sirtuin (SIRT) 1/6 and p50/p65 were determined via the MTT assay and western blotting respectively. The results demonstrated that D‑gal notably increased the proportion of SA‑β‑Gal‑positive cells and decreased the viability of IMR‑90 cells; however, pretreatment with ICA reversed the effects of D‑gal on IMR‑90 cells in a concentration‑dependent manner. Furthermore, it was also demonstrated that the activation of p53/p21 and nuclear factor‑κB (NF‑κB) signaling, and downregulation of SIRT1/6 may be involved in IMR‑90 cells, in D‑gal‑induced aging and ICA may effectively prevent IMR‑90 cells from these changes induced by D‑gal. Taken together, the results of the present study suggest that the anti‑aging molecular mechanisms of ICA may be associated with the regulation of the SIRT1/NF‑κB pathway.