Cancer invasion and metastasis are the leading causes of death. The process of metastasis or tumor cell dissemination is still much of a mystery. Emerging evidence has shown that epithelial-mesenchymal transition (EMT) plays a vital role in the progression of malignant tumor including the inducing cell invasion and metastasis as well as promoting drug resistance. Vinorelbine is a traditional chemotherapeutic agent for treatment of lung cancer and breast cancer by the selectivity to mitotic microtubules. The aim of this study was to investigate the effect of vinorelbine on three metastatic cancer cells including lung cancer (H1975), liver cancer (HepG2), and colon cancer (HCT116) cells through inhibition of metastatic abilities and EMT program. Vinorelbine inhibited the cancer cell proliferation by MTT and colony formation assays and inducing G2/M arrest and cell apoptosis via regulation of Bax, Bcl-2, and Bcl-xL. Vinorelbine decrease the migration and invasion ability of the cancer cells by wound healing assay and Tran swell test. The molecular mechanisms of vinorelbine suppressing the metastatic phenotypes of cancer cells through modulation of E-cadherin, N-cadherin, vimentin and transcription factors Snail, MMP-2 and MMP-9. Our results demonstrated that vinorelbine inhibited the cancer cell metastasis through a reduction in metastatic mobility, such as migration, invasion, and the EMT. It provided the evidence that vinorelbine can be used alone or with other agents for treatment of metastatic lung cancer, liver cancer and colon cancer.Copyright © 2020 Elsevier Masson SAS. All rights reserved.