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DNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses. In this study, we examined single-base resolution methylomes of Populus euphratica under control and salt stress conditions using high-throughput bisulfite sequencing. Our data showed that the methylation levels of methylated cytosines in upstream 2kb, downstream 2kb, and repetitive sequences increased after salt treatment in leaves, but decreased in roots. We also found that heavy methylation in 100-bp upstream of the transcriptional start site repressed gene expression, while methylations within downstream 2K and within the gene body were positively associated with gene expression. A total of 1893 and 1817 significant differentially methylated regions (DMRs) corresponding to 251 and 191 differentially methylated genes (DMGs) were identified in leaf and root tissues, respectively. These DMGs may play important roles in salt stress responses of P. euphratica through the changes of their DNA methylation levels. Overall, these findings provide valuable insights into our understanding of the interaction between gene expression and methylation of salt responses in poplars.