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<i>Objectives:</i> This meta-analysis investigated the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (<i>EGFR</i>) mutations in non-small-cell lung cancer (NSCLC) to clarify whether TTF-1 can be a potential surrogate marker for <i>EGFR</i> mutation status in advanced NSLCL. <i>Methods:</i> A systematic searching of databases, including PubMed, EMBASE, Cochrane Library, and Google Scholar, was performed to identify studies assessing the correlation of TTF-1 expression with EGFR mutations. From 17 studies, 9764 patients were included in the combined analysis of odds ratio (OR) for the correlation between TTF-1 expression and <i>EGFR</i> mutations. <i>Results:</i> Compared with NSCLCs showing negative TTF-1 expression, tumors harboring TTF-1 overexpression showed a significantly higher rate of <i>EGFR</i> mutations (OR = 5.19, 95% confidence interval: 3.60&#8315;7.47, <i>p</i> &lt; 0.00001). This correlation was observed in both subgroups of East Asian (OR = 4.33, 95% CI: 3.46&#8315;5.41, <i>p</i> &lt; 0.00001) and European patients (OR = 4.64, 95% CI: 1.41&#8315;15.28, <i>p</i> &lt; 0.01). In addition, TTF-1 expression was significantly associated with <i>EGFR</i> mutations in exon 19 (OR = 4.63, 95% CI: 2.89&#8315;7.41, <i>p</i> &lt; 0.00001) as well as exon 21 (OR = 3.16, 95% CI: 1.04&#8315;9.60, <i>p</i> = 0.04). <i>Conclusions:</i> This meta-analysis demonstrates a significant correlation between TTF-1 expression and <i>EGFR</i> mutations in patients with NSCLC. The status of TTF-1 expression may be a biomarker to guide anticancer treatment in patients with NSCLC and unknown <i>EGFR</i> mutation status.