The US Food and Drug Administration (FDA) has approved the use of virotherapy. However, significant improvements are anticipated if effective localized infection can be achieved. Herein, we demonstrate magnetic lentivirus is guided by magnetic fields. Introduction of short hairpin RNA (shRNA) into the lentivirus genome enabled micro-scale RNA interference (RNAi) therapy. Although epidermal growth factor receptor (EGFR)-targeted therapies have successfully treated individuals with non-small cell lung cancer (NSCLC) cells, clinical therapeutic outcomes have been compromised by acquired resistance to first-generation tyrosine kinase inhibitors. We assess magnetic lentivirus with NSCLC cells using an in vitro model and achieve micro-scale RNAi through EGFR silencing. This proof-of-principle study demonstrates guided and highly localized micro-scale, RNAi virotherapy.