Potato (Solanum tuberosum L.) is an important food crop and in recent years, Verticillium wilt has become one of the major diseases limiting potato production. To study potato Verticillium wilt, a highly pathogenic strain was isolated from field samples in Heilongjiang. After sequencing and morphological identification, the strain was confirmed as a host-specialized Verticillium nonalfalfae (V. nonalfalfae), Vn011. The genome analysis revealed 151 orphan genes in Vn011, and comparative transcriptomic analysis before and after potato inoculation showed differential expression of 21 genes, including several encoding low-complexity regions (LCRs) and transmembrane (TM) domains. These domains are known to be involved in pathogen signaling, protein folding, and phase separation processes. This study presents the whole-genome sequence of Vn011, having predicted and analyzed the expression changes of orphan genes during the infection process of V. nonalfalfae in potato, and provides new insights into the pathogenic mechanisms of the pathogen. Further research on these orphan genes will not only enhance the understanding of the evolutionary adaptation of V. nonalfalfae, but may also provide new molecular targets for the control of potato wilt disease.