Lung cancer is the leading cause of cancer-related deaths, demanding improvement in current treatment modalities to reduce the mortality rates. Lung cancer is divided into two major classes with non-small cell lung cancer representing ~84% of lung cancer cases. One strategy widely used to treat non-small cell lung cancer patients includes targeting the epidermal growth factor receptor (EGFR) using EGFR-inhibitors, such as erlotinib, gefitinib, and afatinib. However, most patients develop resistance to EGFR-inhibitors within a year post-treatment. Although some mechanisms that drive resistance to EGFR-inhibitors have been identified, there are many cases in which the mechanisms are unknown. Thus, in this study, we examined the role of microRNAs in driving EGFR-inhibitor resistance. As mediators of critical pro-growth pathways, microRNAs are severely dysregulated in multiple diseases, including non-small cell lung cancer where microRNA dysregulation also contributes to drug resistance. In this work, through screening of 2019 mature microRNAs, multiple microRNAs were identified that drive EGFR-inhibitor resistance in non-small cell lung cancer cell lines, including miR-432-5p.