Silk fibroin (SF) is a promising material for biomedical applications especially in the form of nanogels that combine the advantages of nanotechnology and cross-linking gel-like systems with various superior properties in biological environment. The present study describes the preparation of a semi-interpenetrating (semi-IPN) network using SF and polyacrylamide (PAAm) in the presence ofN,N '-methylenebis(acrylamide) (BAAm) as a chemical crosslinker. While the particles were obtained by an inverse microemulsion method, photo-polymerization reactions were performed with Irgacure as an initiator. UV irradiation time and SF concentrations were adjusted to get stable Semi-IPN nanogels with a size smaller than 200 nm. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analyses were used for sample characterizations. FT-IR measurements proved both the existence of SF and PAAM in the nanogel structure and also beta-sheet formation of SF with methanol treatment. A characteristic peak at 20.0 A degrees corresponding to the beta-sheet crystalline structure of SF was obtained by XRD analysis. In addition to the dialysis purification, smaller particles can be obtained with a size around 100 nm by increasing SF concentration. DLS results were supported by TEM images of nanogels with a spherical shape. The results indicated that optimized conditions are suitable for the development of SF nanogels with potential applications in drug delivery.