Emerging mosquito-transmitted RNA viruses, such as ZIKA virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem. ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americans. Although typical ZIKV infection are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other foetal developmental abnormalities. In the last few years, genomic and molecular investigation have established a remarkable progress on the pathogenic mechanism of ZIKV infection using invitro and in vivo models. Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV –mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV. By understanding the mechanism and machinery of ZIKV-host interaction at the cellular level will contribute crucial insights for the development of therapeutics and vaccines.