Thyroid cancer (TC) is the most common endocrine cancer and is a serious health concern due to its aggressiveness and high incidence. Histone modifications affect DNA accessibility and gene transcriptional activity by altering the structure of chromatin. Abnormal histone modifications may affect genome stability and disrupt gene expression patterns, leading to many diseases, including cancer. A growing body of research suggests that histone modifications and TC progression are inextricably linked. This article discusses the impact of aberrant histone modification patterns on TC. By targeting specific histone-modifying enzymes, it may be possible to regulate gene expression and inhibit the growth of TC. Finally, we summarize the relevant histone modification inhibitors to better understand the development stage of the use of these drugs to inhibit histone-modifying enzymes in cancer treatment.