Objective: To investigate the expression of sex-determining region Y-box protein 9 (SOX9) in thyroid cancer and its relationship with clinicopathological characteristics and prognosis of patients. Methods: We retrospectively analysed of 98 patients with thyroid cancer admitted to Nanyang Central Hospital from August 2015 to December 2017; thyroid cancer tissues and paracancerous tissues excised during radical operation were collected as thyroid cancer group and paracancerous group respectively. The expression of SOX9 was detected by real-time quantitative polymerase chain reaction (RT-qPCR) and the expression of SOX9 was detected by immunohistochemistry. According to the expression of SOX9 protein in immunohistochemical staining, patients with thyroid cancer were divided into a positive expression group (67 cases) and a negative expression group (31 cases). The relationship between SOX9 expression and clinicopathological characteristics of patients was observed. All patients with thyroid cancer were followed up for 3 years. Kaplan-Meier method was used to analyze the 3-year cumulative survival rate of patients with thyroid cancer; Log-rank test was used to analyze the single factors related to the overall 3-year survival of patients; COX proportional risk regression model was used to analyze the multiple factors affecting the prognosis of patients. Results: The expression of SOX9 mRNA and protein in thyroid cancer was significantly higher than that in adjacent tissues (P<0.05); the expression of SOX9 was significantly correlated with lymph node metastasis, TNM stage and capsular infiltration (P<0.05); Kaplan-Meier analysis showed that progression-free survival (PFS) and overall survival (OS) in SOX9 negative expression group were significantly higher than those in positive expression group (P<0.05); Log-rank analysis showed that the mean survival time of thyroid cancer patients with high TNM stage, lymph node metastasis, capsular infiltration and SOX9 positive expression was significantly shortened (P<0.05); COX multivariate analysis showed that SOX9 expression and lymph node metastasis were independent risk factors affecting the prognosis of thyroid cancer patients. Conclusion: The expression level of SOX9 in thyroid cancer tissues is significantly increased, and can participate in the occurrence and development of thyroid cancer. The high expression of SOX9 is related to poor prognosis of patients, and can be used as an important indicator to judge the progression of thyroid cancer and prognosis of patients.