Protein kinases (PKs) have central role in extracellular signals mediation. Accordingly, PKs are considered important to Schistosoma mansoni homeostasis maintenance and cellular adaptations since this parasite relies in specific environmental signals to induce responses through sensorial receptors and intracellular proteins. However, the role of these proteins in S. mansoni biology is not well known. This work aims at characterizing the functions of SmFES and SmRAF protein kinases using RNA interference (RNAi) and compounds screening to identifying specific inhibitors. Thus, schistosomula and adult worms were subjected to SmFES and SmRAF knockdown by RNAi. SmFES and SmRAF transcript levels in schistosomula and adult worms were 60%-80% reduced. SmFES knocked-down schistosomula presented significant size reduction (~10%) and 28% of mortality when compared to unspecific control group (GFP). Mice infected with SmRAF knocked-down schistosomula showed a significant decrease in adult worms (27%) and eggs (46%) recovered from the intestine, compared to GFP. Besides, the final section from the small intestine of mice infected with SmFES and SmRAF knocked-down schistosomula presented ~25% more immature eggs than the unspecific control group and histological analyses are underway. Additionally, SmFES and SmRAF protein structures and ATB-binding sites were predicted using Phyre2 software. In silico docking analysis were performed with 80,000 compounds from University of Nottingham MCCC Library. Compounds with predicted affinity with SmFES and SmRAF ATP-binding sites were selected using ChemPLP Score in order to perform an in vitro viability screening in schistosomula and adult worms. These preliminary results demonstrate that SmRAF seems to play a role in S. mansoni development and reproduction during the infection of mammalian host. SmFES seems to be essential to S. mansoni reproduction, egg maturation and schistosomula survival and development in vitro.