In recent years, Zika virus (ZIKV), which causes severe diseases such as congenital microcephaly and Guillain-Barré syndrome, bringing serious harm to humans, has spread throughout the world. However, there are currently no effective drugs against the virus, and the need to develop anti-ZIKV drugs is thus urgent. In this study, we evaluated the antiviral efficacy of cinnamic acid against ZIKV by using reverse transcription-quantitative real-time PCR (qRT-PCR), plaque--forming, immunofluorescence and Western blotting. Additionally, Cinnamic acid possessed anti-ZIKV properties against the post-entry stage of the ZIKV replication cycle, and inhibited RdRp activity. In vivo, we found that cinnamic acid reduced the mortality of mice, viral load in the blood and ZIKV protein levels in the brain. Based on our experiments, cinnamic acid was found to be a potential effective anti-ZIKV drug.Copyright © 2021. Published by Elsevier B.V.