Background: Cell division is regulated by protein kinase B (PKB)-mediated FCH domain only 1 (FCHO1) phosphorylation. Methods: FCHO1560-571, a synthetic water-soluble peptide, was generated from the PKB substrate motif 560PPRRLRSRKVSC571 found in the human FCHO1 protein. Results: In this study, we found that in vitro FCHO1560-571 inhibits cell proliferation via PKB/ERK/SMAD4 pathways in KRAS-mutated A549 lung cancer cells. In addition, FCHO1560-571, at effective doses of 15 and 30 mg/kg, significantly suppressed tumor growth and decreased the size and weight of tumors in A549xenograft mice. Conclusion: These results suggest that the FCHO1560-571 peptide could be a potential therapy for lung cancer. (C) 2020 Elsevier Inc. All rights reserved.