This study investigated the expression of adenosine monophosphate deaminase 1 (AMPD1) in serum of patients with papillary thyroid carcinoma (PTC) and its clinical significance. The expression levels of AMPD1 mRNA in serum of 157 patients with PTC and 100 normal controls were detected by real-time fluorescent quantitative polymerase chain reaction (PCR), and the relationships between expression level of AMPD1 in serum of PTC patients and clinicopathological factors as well as prognosis were analyzed. The results of real-time fluorescent quantitative PCR showed that the expression of AMPD1 mRNA in serum of PTC patients was lower than that in normal human serum (P<0.01). The expression of AMPD1 in serum of PTC patients was not significantly different from the clinicopathological features such as sex, age, lymph node metastasis and the number of lesions (P>0.05); there were distinct differences between its expression and tumor-node-metastasis (TNM) staging and tumor diameter (P<0.05). The single factor Cox analysis revealed that sex, age, number of lesions, TNM staging and the occurrence of lymph node metastasis were significantly correlated with the prognosis of patients (P<0.05). Multivariate Cox analysis showed that TNM staging hazard ratio (HR)=2.93, 95% confidence interval (CI): 1.52-7.04, P=0.015 was an independent prognostic factor in PTC patients. Survival analysis indicated that there was a statistically significant difference in the 5-year overall survival rate between patients with high expression of AMPD1 and those with low expression (P=0.007). In conclusion, the expression of AMPD1 in serum of patients with PTC is closely related to the malignant evolution of PTC and clinical prognosis of patients. AMPD1 is expected to become an important molecule in judging the clinical prognosis of PTC patients, and may become a new target for molecular targeted therapy of PTC.