4‑Methoxydalbergione (4‑MD) can inhibit the progression of certain types of cancer; however, its effects on esophageal cancer (EC) remain unclear. The present study aimed to investigate the inhibitory effect of 4‑MD on EC and its molecular mechanism. ECA‑109 and KYSE‑105 cells were treated with or without lipopolysaccharide (LPS) and 4‑MD. Cell Counting Kit‑8 and colony formation assays were used to analyze cell proliferation. Wound healing assay was performed to evaluate cell migration. ELISA and western blotting were performed to measure the expression levels of NF‑κB and inflammatory cytokines. In cells treated with 4‑MD, proliferation and migration were significantly inhibited, the levels of inflammatory cytokines were downregulated and the NF‑κB signaling pathway was inactivated. Notably, proliferation, migration, inflammation and NF‑κB were promoted by LPS, whereas 4‑MD reversed the increases induced by LPS in EC cells. In conclusion, 4‑MD may attenuate the proliferation and migration of EC cells by inactivating the NF‑κB signaling pathway.