Over recent years, several tissue engineering techniques are used for bone regeneration. In this study gelatin-hydroxyapatite (Gelatin-HA) cryogel scaffolds were used with/without bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-beta 1) to heal critical sized bone defects. Release of growth factors from the cryogels were performed up to 28 days in vitro. Moreover, in vivo study were performed by 6 groups and results were evaluated by micro computerized tomography (mu-CT) and histology on 2 months and 4 months after surgery. Gene expression studies were also performed on 2 weeks and 4 weeks after surgery. Collagen type I (Col I), alkaline phosphatase (ALP) and osteocalcin (OSC) gene expression levels were analyzed. According to histology and mu-CT results, there was a significant bone healing in the BMP-2 containing gelatin-HA cryogel group (Group I) as compared to other groups except autograft applied group (Group IV). Moreover, significant increases were observed for Col I, ALP and OSC in Group I and Group IV. However there was no significant increase in the group of BMP-2 and TGF-beta 1 applied together (Group II). The results reveal that combination of gelatin-HA cryogels with BMP-2 is a promising candidate for healing in critical sized craniofacial bone defects.