As a part of our ongoing research projects, we envisioned the synthesis of 2'-modified-4'-thioRNA, such as 2'-fluoro-4'-thioRNA (2'-F-4'-thioRNA) and 2'-O-methyl-4'-thioRNA (2'-OMe-4'-thioRNA) to enhance the potential of 4'-thioRNA. Appropriately protected 2'-deoxy-2'-fluoro-4'-thiouridine (6), -cytidine (10), and - adenosine (18), substrates for the synthesis of novel modified RNAs were successfully synthesized. The fullymodified RNA consisting of 2'-deoxy-2'-fluoro-4'-thionucleosides was synthesised, and we examined its abilities of hybridization and stability against nucleases. It was found that 2'-F-4'-thioRNA shows high hybridization ability to complementary RNA. Furthermore, 2'-F-4'-thioRNA has strong resistance toward degradation in 50% human plasma.