Purpose: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and accounts for 85–90% of all thyroid cancers. Metastatic differentiated thyroid cancer, radioiodine-refractory thyroid cancer, and anaplastic thyroid cancer still lack effective therapeutic options. Here, we aimed to assess HDAC9 and P300 expression in the papillary thyroid carcinoma cell line and compare them with normal thyroid cells. Methods: Nthy-ori-3–1, a normal thyroid cell line, and BCPAP, a PTC cell line, were cultured for 24 and 48 h and immunofluorescence staining was used to determine the levels of HDAC9 and P300 protein expression. HDAC9 paracrine release was assessed using an ELISA assay. Results: HDAC9 protein expression was higher in both cell groups at the 48th hour than at the 24th hour; however, P300 protein expression was lower in BCPAP cells at the 48th hour than at the 24th hour. In comparison to Nthy-ori-3–1, BCPAP expressed more HDAC9 and P300 proteins. HDAC9 secretion slightly increased in Nthy-ori-3–1 cells from 24 to 48 h. Furthermore, HDAC9 secretion in BCPAP cells dramatically decreased from 24 to 48 h. Conclusion: Our findings revealed that the expression of HDAC9 and P300 was higher in the PTC cell line than in normal thyroid cells. This indicates that the acetylation mechanism in thyroid cancer cells is not the same as it is in healthy cells. Epigenetic studies may reveal the mechanisms underlying PTC with further analysis.