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Protein lysine methyltransferases (PKMT) catalyze methylation of lysine residues on histone tails and non-histone targets. These important post-translational modifications affect the structure and compactness of chromatin, which in turn affects gene expression. There is growing evidence that genetic alterations in PKMT affect the normal expression of PKMT in tissues and thus exert oncogenic or tumor suppressor functions. The expression of PKMT has been found to be associated with the prognosis of tumor patients in a variety of solid tumors. In this review, we summarized the functions of three major PKMT, including EZH2, KMT2 family and SMYD family, and their roles in thyroid carcinoma.