Objective To investigate the expression of discoidin CUB and LCCL domain containing 2(DCBLD2)and mitogen activated protein kinase kinase kinase kinase 3(MAP4K3)in thyroid cancer and their relationship with clinico-pathological features and prognosis.Methods A total of 92 patients with thyroid cancer diagnosed and treated in Xinghua People's Hospital Affiliated to Yangzhou University from January 2016 to June 2020 were selected.Immunohistochemistry(IHC)was used to detect the expression of DCBLD2 and MAP4K3 in thyroid cancer tissues and adjacent tissues.The expression differences of DCBLD2 and MAP4K3 in thyroid cancer patients with different clinicopathological features were compared.Kaplan-Meier curve analysis was used to analyze differences in the progression-free survival prognosis of patients with different DCBLD2 and MAP4K3 expressions.Multivariate COX analysis was used to analyze the risk factors affecting the progression-free survival prognosis of thyroid cancer.Results The positive rates of DCBLD2(67.39%)and MAP4K3(65.22%)in thyroid cancer tissues were higher than those in adjacent tissues(5.43%,6.52%),and the differences were statistically significant(χ2=76.262,68.894,all P<0.05).The expression of DCBLD2 was positively correlated with MAP4K3(r=0.742,P<0.001).The positive rates of DCBLD2 and MAP4K3 in stage Ⅲ～Ⅳ(87.18%,84.62%)and lymph node metastatic cancer tissues(93.75%,90.63%)were higher than those in stage Ⅰ～Ⅱ(52.83%,50.94%)and non lymph node metastatic cancer tissues(53.33%,51.67%),with statistically significant differences(χ2=11.230～15.513,all P<0.05).The 3-year progression-free survival rates of DCBLD2-positive and DCBLD2-negative patients were 74.19%(46/62)and 93.33%(28/30),respectively.The 3-year progression-free survival rates of MAP4K3 positive and negative patients were 75.00%(45/60)and 90.63%(29/32),respectively.The 3-year cumulative progression-free survival rate of DCBLD2 positive group and MAP4K3 positive group was lower than that of DCBLD2 negative group and MAP4K3 negative group,and the differences were statistically significant(χ2=4.533,4.138,P=0.033,0.046).DCBLD2 positive(OR=1.659,P=0.001),MAP4K3 positive(OR=1.606,P=0.001),tumor TNM stage Ⅲ～Ⅳ(OR=1.766,P=0.001)and combined lymph node metastasis(OR=1.868,P=0.001)were independent risk factors for the progression-free survival prognosis of thyroid cancer patients.Conclusion The expressions of DCBLD2 and MAP4K3 were increased in thyroid cancer tissue.They are involved in the occurrence and development of thyroid cancer,which may help evaluate the progression-free survival prognosis of thyroid cancer patients.