The aim of this study was to reveal the changes in the nanostructure of the thermo-sensitive poly(N- isopropylacrylamide-N methacryloyl-(L)-histidine) [poly(NIPA-MAH)] monolithic cryogel with changing temperature around lower critical solution temperature (LCST) of NIPA. Poly(NIPA-MAH) cryogel was prepared by free radical cryopolymerization of NIPA with MAH as a functional comonomer and N,N-methylene- bisacrylamide (MBAAm) as crosslinker directly in a plastic syringe. Cryo-polymerization was initiated by N,N,N,N-tetramethylene diamine (TEMED) and ammonium persulfate (APS) pair at subzero temperature (-16ºC) in an ice bath. LCST of poly(NIPA-MAH) cryogel was found to be 34ºC. The surface morphology and bulk structure of poly(NIPA-MAH) cryogel was revealed with scanning electron microscopy (SEM). Poly(NIPA- MAH) cryogel with 60–100 μm pore diameter has a specific surface area of 42.6 m2/g polymer. Poly(NIPA- MAH) cryogel was characterized by Fourier transform infrared spectrometer (FTIR) and swelling test. The equilibrium swelling degree of poly(NIPA-MAH) cryogel was 22.08 g H2O/g for dry cryogel. The presence of NIPA makes cryogel morpholgy highly porous and differentiates it from conventional gels.