The RNA-binding protein Pumillio-2 (encoded by PUM2) is active during embryonic development and cell differentiation, but possible roles in the dynamic human ovary or in ovarian granulosa cell (GC)-derived tumors, were not known. We studied KGN cells, which are derived from a human GC tumor. We employed siRNA to down-regulate PUM2. A proteomic analysis showed that this treatment reduced not only PUM2 levels but also the abundance of additional 50 proteins, while more than 60 proteins were increased in abundance. GO term analysis revealed that the pathway mainly increased was cell division, a result, which correlated with an increased proliferation rate of siRNA treated KGN cells, as determined by ATP assay and cell counting. Analysis of cell migration (scratch assays) revealed an increased ability to close the gap but unaffected individual cell velocity or migration direction. Taken together, the results indicate a fundamental role of PUM2 in the regulation of ovarian KGN cells. As PUM2 was also detected in primary GC tumor samples, albeit in variable amounts, PUM2 expression may be a novel marker, which may allow to distinguish subsets of GC tumor cells.