Pleural effusion (PE) has been reported useful in many studies for testing epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) with variable results. This systematic review and meta-analysis was performed to elucidate whether PE could be used as a surrogate for tumor tissue to detect EGFR mutations. We extracted 2 × 2 diagnostic table from each included study and calculated data on specificity, sensitivity, negative likelihood ratio (NLR), positive likelihood ratio (PLR) ,and diagnostic odds ratio (DOR). We used the area under curve (AUC) and summary receiver operating characteristic curve (SROC) to summarize the overall diagnostic performance and assessed publication bias by Deeks' funnel plot. Our meta-analysis included 15 eligible publications. The following summary estimates for diagnostic parameters of the EGFR mutations detection in PE were made: sensitivity, 0.86 (95%CI 0.83-0.89); specificity, 0.93 (95%CI 0.91-0.95); PLR, 8.53 (95%CI 5,94-12.25); NLR, 0.18 (95%CI 0.13-0.25); DOR, 63.40 (95%CI 38.83-103.51); and AUC, 0.94. Funnel plot indicated publication bias insignificant. The meta-analysis suggests that EGFR mutation detecting in PE, especially supernatants, is a promising surrogate for tumor tissue in EGFR mutations testing of patients with NSCLC.