Introduction: Citrus is an important fruit crop for human health. The sensitivity of citrus trees to a wide range of abiotic stresses is a major challenge for their overall growth and productivity. Among these abiotic stresses, salinity results in a significant loss of global citrus yield. In order to find straightforward and sustainable solutions for the future and to ensure citrus productivity, it is of paramount importance to decipher the mechanisms responsible for salinity stress tolerance. Thisstudy aimed to investigate how ploidy levels influence salt stress tolerance in citrus by comparing the transcriptomic responses of diploid and tetraploid genotypes. In a previous article we investigated the physiological and biochemical response of four genotypes with different ploidy levels: diploid trifoliate orange (Poncirus trifoliata [L.] Raf.) (PO2x) and Cleopatra mandarin (Citrus reshni Hort. Ex Tan.) (CL2x) and their respective tetraploids (PO4x, CL4x). Methods: In this study, we useda multifactorial gene selection and gene clustering approach to finely dissect the influence of ploidy level on the salt stress response of each genotype. Following transcriptome sequencing, differentially expressed genes (DEGs) were identified in response to salt stress in leaves and roots of the different citrus genotypes. Result and discussion: Gene expression profiles and functional characterization of genes involved in the response to salt stress, as a function of ploidy level and the interaction between stress response and ploidy level, have enabled us to highlight the mechanisms involved in the varieties tested. Saltstress induced overexpression of carbohydrate biosynthesis and cell wall remodelling- related genes specifically in CL4x Ploidy level enhanced oxidative stress response in PO and ion management capacity in both genotypes. Results further highlighted that under stress conditions, only the CL4x genotype up- regulated genes involved in sugar biosynthesis, transport management, cell wall remodelling, hormone signalling, enzyme regulation and antioxidant metabolism. These findings provide crucial insights that could inform breeding strategies for developing salt-tolerant citrus varieties.