As one of the most important fruit tree crops, apple (Malus ×domestica), is faced with the serious impact of soil salinization. However, the underlying genetic and regulatory network remains elusive. Here, we adopted time-course RNA sequencing to decipher the genetic basis and regulatory module of apple in response to salt stress. Among a series of intense changes in genes at each time point, the critical genes in the mitogen-activated protein kinase signaling pathway were highly consistent with the duration of the stress treatment. Moreover, Salt Overly Sensitive 1 (SOS1) genes were identified and predicted to play important roles in the response process. We constructed coexpression modules and explored modules significantly associated with stress. SOS genes were identified in the hub genes, suggesting a critical role. Interestingly, transcription factors were also identified and predicted to cointeract with SOS genes in the hub genes of the coexpression module [e.g., HB7 (MD01G1226600), WRKY33 (MD12G1181000), and ERF106 (MD07G1248700)]. Collectively, our exploration and findings provide a reference and data resource for the study of genetic and salt regulatory networks in apple.