Background <p>Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Despite the favorable prognosis in some patients, there remains a risk of lymph node metastasis and death in some patients. Therefore, new therapeutic strategies are required to improve PTC outcomes.</p> Methods <p>In this study, we performed differential expression analysis using data from patients with PTC collected from the Cancer Genome Atlas program database, and prognostic analysis of differential genes. To understand the effects of ubiquitin-conjugating enzyme 9 (UBC9) on drug therapy, immunotherapy, immune relevance, and gene mutations in tumor cells of patients with PTC, we performed cancer drug susceptibility genomics, computed tumor immune dysfunction and exclusion, tertiary lymphoid tissues, cytolytic activity, immune infiltration, immune modulators, genomic signature differences, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Moreover, we investigated the function of UBC9 in tumor cells using a knockdown assay.</p> Results <p>UBC9 expression level was significantly elevated in the tumor tissues of patients with PTC, and in vitro experiments demonstrated that UBC9 knockdown inhibited tumor proliferation and migration and promoted apoptosis. UBC9 is closely linked to immunity in PTC, and UBC9 may be a potential therapeutic target.</p> Conclusions <p>Our study demonstrated that UBC9 is a novel therapeutic target for PTC and may be a potential strategy for its treatment.</p>