This study aims to investigate the clinical relevance of GOLT1A in papillary thyroid carcinoma (PTC) and evaluate its significance in prognosis of PTC. In this study, 527 data downloaded from the TCGA database and 280 data downloaded from the GTEx database were used for differential gene expression analysis. Univariate and multivariate statistical analyses were performed on the data of 499 PTC patients from the TCGA database and the data of 305 PTC patients subjected to fine-needle aspiration biopsy (FNAB) from the Department of General Surgery of the First Affiliated Hospital of Soochow University and the First Affiliated Hospital of Wenzhou Medical University. In the gene expression of 527 normal tissues and thyroid carcinoma tissues data from the TCGA database and 280 normal tissues from the GTEx database, the expression of GOLT1A was significantly higher in thyroid carcinoma tissues than in normal thyroid tissues (P < 0.001), validated by GEO databases (P < 0.001) and immunohistochemical (IHC) (P < 0.05). Univariate and multivariate analyses of 499 PTC patients and 309 FNAB PTC patients in the TCGA database showed that high expression of GOLT1A was closely related to the poor prognosis of PTC. Specifically, GOLT1A is associated with differentiation risk (P = 0.005), sex (P = 0.006), capsular invasion (P = 0.038) and lateral lymph node metastasis (P < 0.001). In summary, the expression of GOLT1A in thyroid carcinoma tissues was significantly higher than that in normal tissues, and high GOLT1A expression was probably related to the poor prognosis of PTC. GOLT1A is a promising prognostic genetic marker and pathogenic target of PTC.