Background: Some evidence supports that the significance of inflammation is linked to a variety of tumors, including thyroid carcinoma. This work measured the preoperative serum inflammatory factors in thyroid tumors to explore their diagnostic values. Material and Methods: Altogether 487 thyroid tumor patients were recruited, their neutrophil (NE), white blood cell (WBC), monocyte (MO), lymphocyte (LY), platelet (PLT) counts, together with monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), interleukin (IL)-1β, IL-2, IL-27, and tumor necrosis factor-α (TNF-α) levels were compared with controls. Afterward, the receiver operating characteristics (ROC) curve was plotted to further evaluate the values of these inflammatory markers in diagnosis. In addition, multivariable regression analysis was conducted to analyze all these inflammatory factors. Results: Serum PLR, NLR, CRP, and IL-27 levels in thyroid adenoma (TA) and differentiated thyroid carcinoma (DTC) patients were higher than those in controls. Only the areas under the curve (AUC) for CRP and IL-27 were significant in the context of DTC. Besides, the AUC for IL-27 was significant between papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) groups, while that for NLR+PLR was also significant between PTC and healthy control groups. According to multivariable logistic regression analysis, IL-27 and CRP were associated with DTC. Conclusions: Inflammation plays an important role in TA and DTC progression. Preoperative IL-27 and CRP levels help to differentially diagnose DTC. Moreover, IL-27 assists in distinguishing FTC from PTC, and NLR+PLR is important for the differential diagnosis of PTC.