Background and Aims Differentiated thyroid carcinoma (DTC), comprising papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), is the most common type of thyroid cancer. While the majority of DTC patients have a favorable prognosis with standardized treatment, some experience capsular invasion and lymphatic metastasis, leading to poor outcomes. Studies have demonstrated the significant roles of inflammatory and immune factors in tumor progression, but systematic research on their involvement in DTC is lacking. This study aims to analyze the characteristics of cytokines and lymphocyte subsets in DTC patients and their relationships with prognosis.Methods DTC patients treated at the Departments of Thyroid and Breast Surgery of Suzhou Ninth People's Hospital and Ma'anshan 17th Metallurgical Hospital between May 2018 and May 2021 were included, comprising 43 PTC patients and 43 FTC patients. An additional 43 patients diagnosed with benign thyroid nodules (BTN) during the same period served as the control group. The levels of cytokines (TNF-α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-27) and counts of lymphocyte subsets (T lymphocytes, Ts cells, Th cells, B lymphocytes, NK cells) were compared among the three groups before treatment. The relations of cytokines and lymphocyte subsets with clinicopathologic characteristics in DTC patients were analyzed. Changes in cytokines and lymphocyte subsets in DTC patients after surgery were evaluated, and the predictive value of these factors for treatment outcomes was assessed.Results Comparisons among the groups showed that TNF-α, IL-1β, and IL-6 levels were higher in the PTC and FTC groups than that in the BTN group (all P<0.05), with no significant difference between the PTC and FTC groups (P>0.05); IL-2 and IL-8 levels had no significant differences among the three groups (P>0.05); IL-10 levels were lower in the PTC and FTC groups than that in the BTN group, and lower in the FTC group than that in the PTC group (all P<0.05); IL-27 levels were higher in the PTC and FTC groups than that in the BTN group, with higher levels in the PTC group than that in the FTC group (all P<0.05). No significant differences were observed among the three groups in the counts of T lymphocytes, B lymphocytes, or NK cells (all P>0.05); Ts cell counts were higher in the PTC and FTC groups than that in the BTN group and higher in the FTC group than in that the PTC group (all P<0.05); Th cell counts were lower in the PTC and FTC groups than that in the BTN group (both P<0.05), with no significant difference between the PTC and FTC groups (P>0.05). Analysis of relationships between these differential cytokines and lymphocyte subsets with clinicopathologic features of DTC patients revealed that older patients had higher IL-6 levels, patients in advanced stages had higher Ts cell counts, and those with BRAF mutations had lower IL-10 levels (all P<0.05). Postoperative levels of TNF-α, IL-6, IL-27, and Ts cell count were predictive of treatment outcomes in PTC patients (all P<0.05), with AUC values of 0.754, 0.784, 0.781, and 0.754, respectively. For FTC patients, postoperative IL-8, IL-27, and Ts cell count predicted treatment outcomes (all P<0.05), with AUC values of 0.707, 0.788, and 0.715, respectively. For all DTC patients, postoperative TNF-α, IL-27, and Ts cell count were predictive of treatment outcomes (all P<0.05), with AUC values of 0.742, 0.783, and 0.854, respectively.Conclusion Cytokine levels and lymphocyte subset counts exhibit specific characteristics in DTC patients and may be associated with clinicopathological features. Postoperative levels of certain cytokines and lymphocyte subsets have potential predictive value for treatment outcomes in DTC patients.