The APETALA2/Ethylene-Responsive Factor (AP2/ERF) gene family is a transcription factors that is particular to plants. AP2/ERFs plays essential roles in growth and development regulation, biotic and abiotic stressors tolerance, and responding to plant hormones. However, information on the roles of AP2/ERF gene family in Egyptian sugarcane (Saccharum spontaneum) is lacking. In the current study, a genome-wide analysis was performed to identify the AP2/ERF genes in S. spontaneum. Using bioinformatics techniques, 288 SsAP2/ERF have been acquired in total. They were classified into five sub-families based on phylogenetic study, with 14 AP2, 105 DREB, 4 RAV, 143 ERF, 1 Soloist, and 21 ANT. Gene structure, chromosome localization and conserved domain were investigated for SsAP2/ERF genes. As opposed to its homologue genes, which more often express in nodes and buds, tissue-specific expression analysis demonstrated that SsAP2/ERF genes were numerous and expressed ubiquitously in all examined tissues, with slightly higher levels in roots followed by leaves, and flowers. Interestingly, 6 SsAP2/ERF genes that contains two AP2 domains exhibited diverse expression patterns in response to phytohormones including abscisic acid, gibberellic acid, salicylic acid, and methyl jasmonate along with various abiotic stresses such as drought, high salinity, high or low temperature. Concisely, results of this research provide a deep insight towards further functional exploration of the SsAP2/ERFs in response to phytohormone and abiotic stress with the eventual goal of developing crop production.