Background: Previous studies have demonstrated a higher rate of depression in cancer patients harboring KRAS mutations. We evaluated the feasibility of using secondary Electronic Medical Record (EMR) data to examine the association of KRAS mutations with depression in NSCLC patients. Methods: We identified cases with NSCLC from an institutional Cancer Registry. Tumor molecular profiles were obtained as standard of care. Depression was assessed using the Patient Health Questionnaire-2 (PHQ-2), which is part of the institution’s universal Distress Screening tool completed at the time of clinic visit. PHQ-2 score of 2 and above was considered positive for depression. Data was extracted from EMR via Clinical Data Exchange Network bioinformatics tool and confirmed by chart review. Results: Of the 692 NSCLC patients, KRAS status was known in 174 cases: 40 (23%) were KRAS mutated and 134 (77%) were KRAS wild type. 101 (58%) had stage 4 NSCLC. PHQ-2 score was 0 in 146 (83.9%), 1 in 7 (4%), 2 in 19 (10.9%), and > 2 in 2 (1.1%). The rate of positive PHQ-2 for KRAS mutated vs wild type was 15% vs 11% (p = NS). Conclusions: This study in patients with NSCLC did not demonstrate an association between KRAS mutation and depression. Bioinformatics studies harnessing EMR data are a feasible platform to assess the association of genomic data with clinical outcomes and validated algorithms are needed.