Background: Myc-associated zinc finger protein (MAZ) plays a role in cancer progression and metastasis. However, the role and underlying molecular mechanism of MAZ in thyroid cancer have not yet been fully elucidated. This study aimed to explore the clinical significance of MAZ in thyroid cancer tissues, and clarify its mechanism in the occurrence and development of thyroid cancer. Methods: The expression level of MAZ protein in thyroid cancer tissues was detected by bioinformatics analysis and immunohistochemistry (IHC). The relationship between the expression level of MAZ and clinicopathological characteristics of thyroid cancer patients was analyzed by multivariate logistic regression analysis. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of MAZ in thyroid cancer cell lines. After MAZ knockdown cell lines were constructed, wound healing and Transwell assays were used to detect the migratory and invasive abilities of cancer cells. Results: The results of IHC showed that the expression level of MAZ protein in thyroid cancer tissues was higher than that in normal adjacent thyroid tissues (p 0.05), which was consistent with the high expression level of MAZ in thyroid cancer tissues found in The Cancer Genome Atlas (TCGA) database. The results of multivariate logistic regression analysis indicated that the expression level of MAZ was correlated with tumor diameter and tumor capsule of thyroid cancer patients. Moreover, patients with the high MAZ expression level had shorter overall and disease-free survival compared with thyroid cancer patients with the low MAZ expression level (p 0.05). Further cell function assays indicated that downregulation of MAZ expression level could inhibit the migration and invasion of thyroid cancer cell lines. Moreover, the expression level of epithelial-mesenchymal transition (EMT)-related factor fibronectin 1 (FN1) was obtained from the RNA-seq of MAZ knockdown in thyroid cancer cells. RT-qPCR confirmed that the expression level of FN1 was elevated in MAZ knockdown cell lines (p 0.05). Bioinformatics analysis indicated that the expression level of FN1 was upregulated in thyroid cancer tissues and had a negative relationship with the expression level of MAZ, as evidenced by correlation analysis. Conclusions: A high expression level of MAZ in thyroid cancer tissues was associated with a poor prognosis of patients. MAZ could affect the progression of thyroid cancer by inducing the EMT process.