The Tibetan fox (Vulpes ferrilata) belongs to Canidae of Carnivorous Order and is one of the unique species on the Qinghai-Tibet Plateau. However, the molecular mechanism of its adaptation to high altitude is still unclear. Here, we applied Oxford Nanopore sequencing and Hi-C technology to assemble the chromosome-level draft genome of V. ferrilata. A 2.38-Gb genome with an N50 length of 133.96 Mb was obtained. The proportion of repeated sequences is 33.77%. The 157 contigs were further assembled into 18 chromosomes with a sequence length of 2378.42 Mb, accounting for 99.95% of the total length. Phylogenetic analysis showed that the Tibetan fox formed a clade with the red fox, with an estimated divergence time of 3.27 MYA. However, the significantly over-represented pathways and significantly enriched GO-terms of expanded gene families in V. ferrilata genome were mainly related to hypoxia response and energy metabolism, which indicated a mechanism strategy of V. ferrilata for high-altitude adaption. Furthermore, the selection signature analysis identified genes associated with oxygen transport, DNA damage and repair, and angiogenesis in V. ferrilata when compared with the other relative species. The construction of the genome of V. ferrilata provided valuable information for the further genetic mechanism analysis of important biological processes and will facilitate the research of genetic changes during evolution.