In adults, Uveal melanoma (UM) is a common primary intraocular malignancy with high mortality rate due to liver metastasis. Epidemiology and pathogenesis of liver metastasis in UM are not explored and no effective therapy is currently available for UM. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. Earlier, IGF-1 receptor was found to be highly expressed in UM, which is related to tumor prognosis. FoxO3a is a Forkhead box O (FOXO) transcription factor and a downstream target of IGF-1R/PI3K/Akt pathway involved in a number of pathophysiological processes including cancer. However, the role of FoxO3a in UM is unknown. In this study, we investigated the involvement of FoxO3a in migration and invasion of UM. Western blot analysis showed that IGF-1 led to activation of Akt and concomitant phosphorylation of FoxO3a which is associated with its translocation into the cytoplasm from the nucleus and its functional inhibition led to the inhibition of expression of Bim and p27, but an increase in the expression of Cyclin D1. The effects of IGF-1 on UM cells were reversed by PI3K inhibitor LY294002 or Akt siRNA, and overexpression of FoxO3a also attenuated basal invasion and migration of UM. Taken altogether, these findings suggest that inhibition of FoxO3a by IGF-1 via PI3K/Akt pathway has an important role in IGF-1 induced proliferation and invasion of UM. These results also suggest that FoxO3a and IGF signaling may represent a valid target for investigating the development of new strategies for treatment and prevention of pathology of UM.