The present study is to measure serum contents of matrix metalloproteinase (MMP)-2 and MMP-9 in Papillary Thyroid Carcinoma (PTC) patients before and after Radiofrequency Ablation (RFA), and to evaluate the correlation of MMP-2 and MMP-9 contents with prognosis. A total of 41 PTC patients who received ultrasound-guided percutaneous RFA between May 2015 and Oct 2016 were included. The number of foci were 96. Before surgery, the number, size, property, echo, boundary, shape, calcification, peripheral sound halo and blood flow distribution of thyroid nodules were examined using ultrasound. Enzyme-linked immunosorbent assay was used to measure the serum contents of MMP-2 and MMP-9 before and after RFA. Logistic regression analysis was performed to identify independent risk factors for the prognosis of PTC and to investigate the correlation of MMP-2 and MMP-9 contents with prognosis. The medians of MMP-2 and MMP-9 contents were used as the thresholds that discriminated low and high levels of MMP-2 and MMP-9, respectively. The effect of low or high levels of MMP-2 and MMP-9 on prognosis was evaluated by Kaplan-Meier analysis. Ultrasound showed that RFA effectively reduced tumor foci and the surrounding blood supply. ELISA showed that serum contents of MMP-2 and MMP-9 in PTC patients were significantly reduced after RFA. Logistic regression analysis demonstrated that age, calcification degree, regularity of shapes, and diameter and number of foci in PTC patients were effective independent risk factors for the prognosis after RFA. In addition, serum contents of MMP-2 and MMP-9 were correlated with independent risk factors for the prognosis of PTC patients after RFA. Of note, PTC patients with high MMP-2 or MMP-9 contents had poorer prognosis than those with low MMP-2 or MMP-9 contents. The present study demonstrates that serum contents of MMP-2 and MMP-9 have clinical significance for the evaluation of PTC prognosis after RFA.