Esophageal cancer (EC) is one of the malignant cancer with pool survival due to the limited therapeutic and drug-resistance. Narciclasine, a natural compound from Lycoris sanguinea possesses antitumor and anti-inflammatory properties. However, the mechanisms underlying the growth-inhibitory effect of narciclasine against EC have not yet been elucidated. Experimental evidences indicated that narciclasine treatment significantly affected the distribution of FAK and its phosphorylation, resulting in proliferation inhibition and migration inhibition of EC. Our study also showed that narciclasine treatment triggered DNA damage and inhibited DNA replication, leading to cell cycle arrest and apoptosis. Further mechanistic studies indicated that narciclasine inhibited EC cell proliferation and migration through FAK/JNK and p38 pathway. Altogether, these findings suggest that narciclasine could be a potential novel chemotherapeutic agent for esophageal cancer cell proliferation and migration. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved.