c-Fos protein has a function in different types of cancers and is expressed mostly in neurons. It is a human homolog of the viral oncogene. c-Fos is a member of the FOS gene family, these genes interact with the JUN family member to form transcription factors and play a major role in neurons cell development. These genes were also used as an early marker, in neuronal cells to determine early growth and functional features of the neuroendocrine system. Losses in gene function due to mutation leads to neuronal death and have a function in apoptosis. This study has performed mutational conservation in the c-Fos gene across different species. the c-Fos protein sequence was retrieved from the UniProt database (P01100). Total forty nine (49) homologous sequences with the c-Fos protein sequence were identified using the BLASTp tool. Multiple sequence alignment (MSA) and phylogenetic tree construction was done using the MEGA tool. The phylogenetic tree shows that the c-Fos protein of Homosapiens was closely related to Pan troglodytes. UPGMA tree also shows the evolutionary relationship between c-Fos proteins and with the other 49 species included in the dataset. Evolutionary study shows that Myotis species was the common evolutionary species and predicted as root for all other species hence c-Fos gene might have an evolutionary link with these species. Myotis are the most wide diverged species and belongs to the genus of bats. This study highlights the similarity and evolutionary relationship of the c-Fos gene. In this research detailed analysis of evolutionary analysis, PPI, GO, Disease Enrichment was done to understand the functional and evolutionary aspects of c-FOS protein. This study identifies the evolutionary relationship, protein-protein interaction and pathway enrichment of the c-FOS protein. This research can be further extended to include ligand screening and identification of potential ligand against c-FOS protein for drug development and discovery.