Initiation and recurrence of lung cancer, the most fatal cancer worldwide, are attributed to lung cancer stem cells (CSCs). Evidence suggests that cancer cells can be turned into CSCs in a spontaneous way, and therefore simultaneous elimination of lung CSCs and cancer cells is crucial to achieve effective therapy of lung cancer. In lung cancer, epidermal growth factor receptor (EGFR) is overexpressed in both CSCs and cancer cells. The present study developed salinomycin poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles conjugated with EGFR aptamers (M-SAL-EGFR) to kill lung CSCs and cancer cells. The 24 nm sized M-SAL-EGFR was prepared by a lipid film based method. The EGFR was overexpressed in lung CSCs and cancer cells. Results revealed that the M-SAL-EGFR could efficiently bind to EGFR-overexpressing lung CSCs and cancer cells, and induced enhanced cyotoxic effect than non-targeted M-SAL and salinomycin. Administration of M-SAL-EGFR in mice with lung cancer xenograft inhibited tumor growth more effectively compared with M-SAL and salinomycin. The EGFR aptamers were thus able to promote effective salinomycin delivery to lung cancer. Our results also suggest that the M-SAL-EGFR represents a promising approach for targeting both lung CSCs and cancer cells.