HOX genes have been well described as important players in development and morphogenesis, and more recently, in carcinogenesis. The role and clinical implication of homeodomain-containing gene 10 (HOXC10) in human thyroid cancer is poorly understood. Real-time PCR and bioinformatics analysis were used to detect the expression of HOXC10 in normal and human thyroid cancer samples from Shanghai General Hospital (also known as Shanghai First People's Hospital) and the TCGA dataset. The survival time of patients with human thyroid cancer was also detected. Cell Count Kit-8 (CCK8) analysis was used to detect cell proliferation, and the cell cycle was assessed by flow cytometry. Migration and invasion were detected by transwell analysis. Gene set enrichment analysis (GSEA) was used to explore the correlation of HOXC10 with signaling pathways. Real-time PCR and Western blot analysis were used to detect the expression of signaling pathway related genes in human thyroid cancer cells. HOXC10 expression in Shanghai General Hospital and the TCGA dataset revealed a significant increase in human thyroid cancer tissues and its expression was positively correlated with the advanced age, poor pathologic stage, and poor prognosis. HOXC10 knockdown by shRNA conferred cell cycle blocking and inhibition of migration and invasion. GSEA in the TCGA datasets revealed that HOXC10 expression was positively correlated with cytokine-cytokine receptor interaction and chemokine signaling pathways. Our data suggest that inhibition of HOXC10 may be a therapeutic strategy for human thyroid cancer treatment. This study investigates the role and clinical implication of HOXC10 in human thyroid cancer.