BackgroundThyroid cancer-related deaths mostly result from metastasis. It was reported that the immunometabolism associated enzyme interleukin-4-induced-1 (IL4I1) was related to tumor metastasis. The present study was intended to investigate the effects ofIL4I1on thyroid cancer metastasis and its relationship with the prognosis.MethodsData from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to find out the different mRNA expressions ofIL4I1between thyroid cancer and normal tissues. And Human Protein Atlas (HPA) was used to assess IL4I1 protein expression. To further differentiate thyroid cancer from normal tissues and estimate the impact ofIL4I1on the prognosis, the receiver operating characteristic curve (ROC) and Kaplan–Meier (KM) method was performed. The protein–protein interaction (PPI) network was established using STRING, and functional enrichment analyses were conducted by “clusterProfiler” package. Then, we assayed the correlation betweenIL4I1and some related molecules. The relationship betweenIL4I1and immune infiltration was performed using “Gene Set Variation Analysis (GSVA)” package in TCGA and tumor-immune system interaction database (TISIDB). Finally, we did in vitro experiments in order to further prove the bioeffects ofIL4I1on metastasis.ResultsThe expression ofIL4I1mRNA and IL4I1 protein was significantly upregulated in thyroid cancer tissues. The increment ofIL4I1mRNA expression was related to high-grade malignancy, lymph node metastases and extrathyroidal extension. The ROC curve displayed the cutoff value of 0.782, with the sensitivity of 77.5% and the specificity of 77.8%. KM survival analysis showed that there was a worse PFS in patients with highIL4I1expression than those with lowIL4I1expression (p= 0.013). Further study indicated thatIL4I1was associated with lactate, body fluid secretion, positive regulation of T cell differentiation, and cellular response to nutrients in Gene Ontology (GO) analysis. Moreover,IL4I1was found correlated with immune infiltration. Finally, the in vitro experiments revealed the promotion ofIL4I1on cancer cell proliferation, migration and invasion.ConclusionsThe increasedIL4I1expression is markedly correlated with the immune imbalance in the tumor microenvironment (TME) and predicts poor survival in thyroid cancer. This study reveals the potential clinical biomarker of poor prognosis and the target of immune therapy in thyroid cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12902-023-01407-1.