In this study, a microfluidic method to generate small polymeric particles (approximate to 10 mu m in diameter) via the control of interfacial tension without using oil and in situ photopolymerization immediately after drop generation was introduced. For the reduction in size, the selection of proper sample and sheath liquid to minimize the interfacial tension is extremely important, and 4-HBA (4-hydroxybutyl acrylate) and PVA (poly(vinyl acrylate)) were employed as core and sheath fluid pair because of much smaller surface tension than the case using oil. In addition, PVA is easily washable by aqueous solution, which is a strong advantage when the particle is applied in biomedical fields. The viscosity effect of sheath flow was also examined for further size reduction. The loading and release properties of proteins were evaluated using fluorescently labeled bovine serum albumin for the potential application as drug carrier. The protein was uniformly loaded into particles, and the protein release rate was dependent oil the particle size. For utility in the biomedical area, the cyto-compatibility test of 4-HBA was performed by culturing glioma cells oil the 4-HBA sheet, and the cells were alive well after 4 days Culture. Conclusively, this oil-free particle generation methods facilitates the generation of uniform and small particles in a simple way without all oil-washing process.