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Epidermal growth factor receptor (EGFR) mutant lung cancers tend to respond well to EGFR tyrosine kinase inhibitors (TKIs). However, resistance has been described. Molecular studies have revealed that concurrent mutations of tumor driver genes are associated with TKI resistance. To delineate the role of concurrent mutation of tumor suppressor gene p53 in TKI resistance, a meta-analysis was performed using published observations of EGFR mutant lung cancer patients treated with first or second generation TKIs. 31 studies are included in the analysis following a search of PubMed. Probability of TKI resistance and progress free survival (PFS) were compared in patients with or without p53 mutation. An increased probability of TKI resistance is seen in p53 mutant lung cancers. Interestingly, when resistance is defined as PFSmonths, there is insignificant increase of resistance in p53 mutant patients (OR=1.93, 95% CI [0.38, 9.85], p=0.43). When resistance is defined as PFS(OR=20.16, 95% CI [2.61, 155.75], p=0.004). In addition, p53 mutation is associated with a significantly shortened progress free survival in these patients (HR=1.57, 95% CI [1.26,1.97], p<0.0001).