The invention belongs to the pharmaceutical field, and relates to a preparation method and pharmaceutical application of a fluorinated analogue of natural marine product cyclodepsipeptide (namely natural marine product Largazole) shown in the formula (I). The inhibitory activity test of HDACs in vitro shows that the compound of the invention has a strong and selective inhibitory effect on HDACs. Furthermore, drugs or compositions containing the compound of the present invention can be used to prepare anti-tumor therapeutic agents. The formula is shown in the description.