Objective: To further investigate TACSTD2 and SPP1 gene mRNA expression in thyroid carcinoma and their association with patients' prognosis and clinical pathological characteristics by data mining of the Oncomine and Kaplan-Meier plotter databases. Methods: TACSTD2 and SPP1 mRNA expression data from thyroid carcinoma were retrieved from the Oncomine database and further analyzed by comparing tumor tissue with corresponding normal tissue. The prognostic significance of TACSTD2 and SPP1 mRNA in thyroid carcinoma were evaluated by the online survival analysis tool "Kaplan-Meier Plotter" (KM plotter) database. Fifty-one patients with thyroid carcinoma who received surgery were retrospectively analyzed. The TACSTD2 and SPP1 protein expression in cancer tissue and normal thyroid tissue were examined by immunohistochemical assay. The correlation between TACSTD2, SPP1 protein expression and patients' clinicopathological characteristics were also evaluated. Results: Four analyses compared the TACSTD2 gene expression between thyroid cancer and normal tissue were included in the present work. The pooled results showed that TACSTD2 mRNA expression levels in thyroid carcinoma tissue was significantly higher than that of normal thyroid tissue (p=0.003). For SPP1, the combined analysis from 8 analyses demonstrated that SPP1 mRNA level in thyroid carcinoma was up regulated compared to normal tissue with statistical significance (p<0.05). A significant difference of overall survival (OS) between TACSTD2 high and low expression groups was found in thyroid carcinoma patients (HR=0.17, 95% CI: 0.04-0.74, p=0.0078). However, for the SPP1 gene the difference was not statistically different between high and low mRNA expression groups (HR=0.062, 95% CI: 0.23-1.71, p=0.35). TACSTD2 interacted with TGFBI, MAP3K11, RAB13, MMP2, CHD1, KRT19, KRTAP5-2, ZNF92, C1QBP, and CYP8B1, which are related to cell proliferation and cellular protein metabolic pathways. The protein coded by SPP1 interacted with FGF2, RUNX2, IGF1, INS, VEGFA, IL6, MMP13, PTH, SP7, and BMP2, which are related to epithelial cell to mesenchymal cell transition (EMT), cell proliferation and negative regulation of apoptotic processes. Immunohistochemical analysis showed that TACSTD2 positive expression was correlated with the tumor capsular invasion (p<0.05) and lymph node metastasis (p<0.05). SPP1 positive expression was correlated with lymph node metastasis (p<0.05). Conclusion: TACSTD2 and SPP1 mRNA expression were up-regulated in cancer tissue compared to normal thyroid tissue in thyroid carcinoma. High level TACSTD2 mRNA was associated with poor prognosis.