Monodispersed poly (N-isopropylacrylamide) (PNIPA) nanoparticles and their derivative poly (N-isopropylacrylamide-co-acrylic acid) (PNIPA-co-AA) nanoparticles were successfully synthesized. Regulation of the size and the lower critical solution temperature (LCST) of the hydrogel nanoparticles was intensively studied. The results showed that the diameters and LCST of the particles can be arbitrarily manipulated according to different application designs. The relationship between the size of the particles and the amount of surfactant were quantitatively disclosed. It was found that the LCST of PNIPA-co-AA nanoparticles ranging from 35-45 degrees C correlated with the molar fraction of acrylic acid which was copolymerized with NIPA. The pH sensitivity of PNIPA-co-AA nanoparticles was displayed by the transmittance transition of their aqueous solution in various pH conditions. Furthermore, the anti-cancer drug 5-fluorouracil (5-Fu) was first loaded into both PNIPA and PNIPA-co-AA hydrogel nanoparticles with an entrapment efficiency larger than 4%. In vitro release of 5-Fu from PNIPA-co-AA nanoparticle hydrogels was shown to be pH- and temperature-dependent, which demonstrated that the PNIPA-co-AA nanoparticles have great potential in the design of controlled drug delivery systems.