Organic–inorganic hybridized nanofibers constituted of gelatin and siloxane were generated by the electrospinning technique for use as bone regeneration matrices. The composition of the nanofibers selected was to be both degradable and bioactive. Precursors of gelatin and siloxane were dissolved in a modified acidic solvent composed of acetic acid, ethyl acetate, and distilled water. The hybridized nanofibers with various compositions (gelatin/siloxane = 1/2, 1, and 2 by weight fraction) were successfully electrospun under the adjusted processing conditions. Compared to the pure gelatin nanofiber, the hybridized nanofibers showed improved chemical stability in a saline solution. This was attributed to the cross‐linking effect of the siloxane with the gelatin chains. Osteoblastic cells were observed to attach, spread, and populate actively on the hybridized nanofiber matrices. In particular, the cells on the hybridized nanofibers were recruited to elicit better osteoblastic activity (alkaline phosphatase) with respect to those on the pure gelatin. The newly‐developed hybridized nanofiber is considered to be useful as a bone regeneration matrix, due to its nanofibrous structural trait as well as its degradability and bone cell activity. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008