Biodegradable microspheres have been gathering attention as a promising controlled release drug delivery system (DDS), since they can administrate with one injection, dissolve in a body, release drugs over time, and do not need to remove after use. To produce microspheres with high throughput and high uniformity, flowfocusing microfluidic devices have been widely employed. Although softlithography technology is a simply way to replicate flow-focusing microfluidic devices, there has yet to be reported organic-solvent resistant, flowfocusing microfluidic devices mainly due to lack of organic-solvent resistant elastomers. Here, we establish a method to fabricate flow-focusing microfluidic device using fluoroelastomer, SIFEL. We stacked a vinyl silicone end group rich layer and a silicone hybrid end group rich layer to seal SIFEL microfluidic devices by using hydrosilylation between two layers. Then, by flowing chloroform, we experimentally verified that SIFEL microfluidic devices did not swell, whereas polydimethylsiloxane (PDMS) microfluidic device showed swelling. When we flowed polyvinyl alcohol (PVA) 1% aqueous solution flow in continuous phase and 1% poly lacticco-glycolic acid (PLGA) in chloroform flow in discontinuous phase, we obtained PGLA microspheres with diameter of 67.0±1.6 μm. Therefore, we envision that the SIFEL device can be a powerful tool for development of controlled-release DDS for water insoluble drugs.