Gelatin nanofibers can be used in the development of a biomimicking artificial extra cellular matrix(ECM) for tissue engineering, wound healing dressings and drug release. However, gelatin nanofibers are water soluble and have weak mechanical strength. Two different cross-linking methods for preparing gelatin nanofibers were used to render gelatin nanofibres insoluble: 1) UV radiation for modified gelatin nanofibers by trans-cinnamic acid; and 2) electrospun gelatin nanofibers cross-linked with genipin. A photo cross-linking method was used to examine the effects of ultraviolet (UV) radiation on the modified gelatin nanofiber scaffolds. A modified gelatin solution containing gelatin, trans-cinnamic acid and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) at a molar ratio of 1:3:30 was prepared. The results showed that the degree of modification in gelatin molecules was 14.5 groups per mol. The modified gelatin was dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol at 20%(w/v) and nanofibrous meshes were obtained by electrospinning. After drying, the nanofibrous meshes were exposed to a commercial germicide UV (=254 nm) lamp for different times. The swelling ratio of each nanofibrous mesh was decreased from 195% to 105% with increasing UV exposure time from 1 h to 10 h. A cross-linking agent method was used to evaluate the effects of the cross-linked gelatin nanofiber scaffolds with genipin. The swelling ratios decreased from 725% to 445% with increasing genipin solution concentration from 0.5%(w/v) to 2%(w/v). The results of the cell culture suggest that cross-linking gelatin nanofibers with 0.5%(w/v) genipin improves the level of cell proliferation with increasing cell culture time from 1 day to 5 days. Moreover, the cell viability of each nanofiber increased with increasing cell culture time. However, the cell viability decreased with increasing genipin solution concentration.