<jats:sec><jats:title>Objectives</jats:title><jats:p>This study aimed to explore the diagnostic significance of <jats:sup>18</jats:sup>F-fluorodeoxyglucose (<jats:sup>18</jats:sup>F-FDG) positron emission tomography (PET)/CT for predicting the presence of epidermal growth factor receptor (<jats:italic>EGFR</jats:italic>) mutations in patients with non-small cell lung cancer (NSCLC).</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>A systematic review and meta-analysis.</jats:p></jats:sec><jats:sec><jats:title>Data sources</jats:title><jats:p>The PubMed, EMBASE and Cochrane library databases were searched from the earliest available date to December 2020.</jats:p></jats:sec><jats:sec><jats:title>Eligibility criteria for selecting studies</jats:title><jats:p>The review included primary studies that compared the mean maximum of standard uptake value (SUV<jats:sub>max</jats:sub>) between wild-type and mutant <jats:italic>EGFR</jats:italic>, and evaluated the diagnostic value of <jats:sup>18</jats:sup>F-FDG PET/CT using SUV<jats:sub>max</jats:sub> for prediction of <jats:italic>EGFR</jats:italic> status in patients with NSCLC.</jats:p></jats:sec><jats:sec><jats:title>Data extraction and synthesis</jats:title><jats:p>The main analysis was to assess the sensitivity and specificity, the positive diagnostic likelihood ratio (DLR+) and DLR−, as well as the diagnostic OR (DOR) of SUV<jats:sub>max</jats:sub> in prediction of <jats:italic>EGFR</jats:italic> mutations. Each data point of the summary receiver operator characteristic (SROC) graph was derived from a separate study. A random effects model was used for statistical analysis of the data, and then diagnostic performance for prediction was further assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Across 15 studies (3574 patients), the pooled sensitivity for <jats:sup>18</jats:sup>F-FDG PET/CT was 0.70 (95% CI 0.60 to 0.79) with a pooled specificity of 0.59 (95% CI 0.52 to 0.66). The overall DLR+ was 1.74 (95% CI 1.49 to 2.03) and DLR− was 0.50 (95% CI 0.38 to 0.65). The pooled DOR was 3.50 (95% CI 2.37 to 5.17). The area under the SROC curve was 0.68 (95% CI 0.64 to 0.72). The likelihood ratio scatter plot based on average sensitivity and specificity was in the lower right quadrant.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Meta-analysis results showed <jats:sup>18</jats:sup>F-FDG PET/CT had low pooled sensitivity and specificity. The low DOR and the likelihood ratio scatter plot indicated that <jats:sup>18</jats:sup>F-FDG PET/CT should be used with caution when predicting <jats:italic>EGFR</jats:italic> mutations in patients with NSCLC.</jats:p></jats:sec>