Objective To analysis the expression of thyroid transcription factor 1 (TTF-1) in patients with lung adenocarcinoma, and discuss the relationship between TTF-1 expression and prognosis of patients with advanced lung adenocarcinoma. Methods A total of 786 cases of lung adenocarcinoma who were admitted to Xi'an Chest Hospital from January 2012 to June 2016 were selected. The expression of TTF-1 was detected by immunohistochemistry. The relationship between TTF-1 expression and patients ' clinicopathological features, treatment and survival were analyzed. Cox proportional hazard model was used to analyze the relationship between TTF-1 and prognosis of patients with advanced lung adenocarcinoma. Results Among 786 patients, 559 patients (71.12％) had positive TTF-1 expression, 227 patients (28.88％) had negative TTF-1 expression. The expression rates of TTF-1 in patients with well-differentiated, early stage, no lymph node metastasis, and no distant metastasis [77.26％ (197/255), 78.89％ (269/341), 78.95％ (225/285), and 75.61％(372/492)] were higher than those in patients with poorly differentiated, late stage, lymph node metastasis and distant metastasis 68.17％ (362/531), 65.17％ (290/445), 66.67％ (334/501), 63.60％ (187/294), the differenceswere statistically significant (χ 2 values were 6.917, 25.261, 13.339, and 12.911, all P < 0.05). The expressions of TTF-1 in primary lesions and metastatic lesions were consistent (κ = 0.894, P < 0.01). Among 385 patients with advanced lung adenocarcinoma who were unable to perform the operation, the proportion of epidermal growth factor receptor (EGFR) mutation in TTF-1 positive expression patients (45.60％, 109/239) was significantly higher than that in TTF-1 negative expression patients (26.02％, 38/146), and the difference was statistically significant (χ 2 = 14.721, P < 0.01). The median progression free survival (PFS) time of TTF-1 positive expression patients was significantly longer than that of TTF -1 negative expression patients (6.00 months vs. 4.20 months, P < 0.01), whether EGFR was mutation or not, the median PFS time of TTF-1 positive expression patients was significantly longer than that of TTF-1 negative expression patients (P =0.003; P < 0.01). TTF-1 expression (HR = 0.793, 95％ CI 0.639-0.984, P = 0.011) and EGFR gene status (HR =0.694, 95％ CI 0.432-0.864, P = 0.004) were independent influencing factors affecting the PFS of patients with advanced lung adenocarcinoma. Conclusions TTF-1 is widely expressed in lung adenocarcinoma and is associated with tumor differentiation, staging, lymph metastasis and distant metastasis. TTF-1 is a prognostic influencing factor in patients with advanced lung adenocarcinoma and can be used as a predictor of treatment for patients with advanced lung adenocarcinoma.