[Objective] The aim of this study was to investigate prokaryotic microbial community structures and salt-tolerant genes in hypersaline sediments from Huama salt lake, Northern Shaanxi, China. [Methods] We constructed 16S rRNA library and fosmid library using metagenome of the sediment, and detected prokaryotic microbial distribution and salt-tolerant genes by high-throughput pyrosequencing and bioinformatic analysis. [Results] In total 18978 high-quality reads for 16S rRNA were assigned to 23 phyla, 155 genera and 5221 OTUs. Euryarchaeota and Proteobacteria were the dominant phyla. Sixteen dominant genera such as Halorhabdus, Halorubrum and Pseudomonas and 139 infrequent ones like Halomonas, Psychroflexus and Acinetobacter were explored. A total of 37 salt-tolerant strains were detected from the metagenomic DNA fosmid library containing 4126 strains. The salt-tolerant strains like 5-5, 2E4 and 2F4 exhibited strong tolerance against stresses caused by NaCl, CuSO₄, ZnSO₄ and CdSO₄. High-throughput pyrosequencing of the metagenomic fragment in the strain 5-5 explored 61 unigenes, 23 homogenous genes encoding salt-, or other stress-tolerant proteins in other biological cells, such as inorganic pyrophosphatase, transposase, tellurite resistance protein and calmodulin. [Conclusion] Hypersaline sediments in salt lakes harbor diverse bacterial and arhaeal community and rich salt-tolerant genes.