Objective:To investigate the origin and distribution of IL-9 derived cells in patients with different types of thyroid cancer.Methods:Patients with papillary thyroid carcinoma(22 cases)and medullary thyroid carcinoma(8 cases)were recruited from March 2021 to December 2023, along with 30 healthy individuals undergoing physical examinations as controls. Blood samples were collected preoperatively and within 7 days postoperatively from the thyroid cancer patients and the controls. The expression of IL-9 in peripheral blood mononuclear cells(PBMCs)was measured using flow cytometry. The levels of cytokines IL-13, IL-4, IL-33, IL-25, IL-1β, IL-9, and IL-21 in serum were determined through enzyme-linked immunosorbent assay(ELISA). The mRNA levels of PU.1, SMAD2, TGF-β, and STAT3 in blood cells were measured via quantitative real-time PCR(qRT-PCR). During surgeries, thyroid cancer tissue and adjacent normal tissue samples were obtained. The mRNA expression levels of IL-25, IL-33, IL-1β, IL-13, RORα, and IL-9 in tissues were detected by qRT-PCR. Immunofluorescence staining was applied to analyze IL-9 expression in cancerous and adjacent normal tissues.Results:Flow cytometry showed that the distribution frequency of IL-9-producing T cells(Th9 cells)was higher in papillary thyroid carcinoma patients than those in medullary thyroid carcinoma patients, and higher in medullary thyroid carcinoma patients than those in the control group. After surgery, the distribution frequency of Th9 cells increased significantly in both papillary thyroid carcinoma and medullary thyroid carcinoma groups. However, the distribution of type 2 innate lymphoid cells(ILC2s)producing IL-9 showed no significant difference among the groups. Preoperatively, papillary thyroid carcinoma and medullary thyroid carcinoma patients had significantly higher serum levels of IL-9, IL-33, IL-25, IL-1β, IL-4, and IL-21 than the control group. Postoperatively, IL-9 and IL-4 levels increased further, while IL-33 and IL-25 levels decreased significantly. qRT-PCR revealed that the mRNA expression of Th9-related transcription factors PU.1, SMAD2, TGF-β, and STAT3 was lowest in the control group and increased significantly after surgery in thyroid cancer patients. In cancer tissue, qRT-PCR showed that IL-25 and IL-33 mRNA expression in medullary thyroid carcinoma and papillary thyroid carcinoma were significantly higher than those in adjacent tissues, and the medullary thyroid carcinoma was significantly higher than that in papillary thyroid carcinoma tissues. Contrastedly IL-9 and IL-1β mRNA expression were decreased. Immunofluorescence staining showed that IL-9 expression was lower in cancer tissue than in adjacent normal tissue and was mainly located in CD4⁺T cells.Conclusion:IL-9 derived from Th9 plays an anti-tumor role in patients with thyroid cancer. The presence and distribution of Th9 cells correlate with the malignancy of thyroid cancer. IL-9 and Th9 cell may be considered as promising new targets for the diagnosis and therapeutic monitoring of thyroid cancer.