Epidermal　growth　factor　receptor　(EGFR)　exon　19　deletions　are　a　common　mutation　that　can　lead　to　non-small　cell　lung　cancer　(NSCLC).　Here,　we　designed　and　synthesized　Au　clusters　coated　with　EGFR-target　peptides　to　treat　EGFR　exon　19　deletions　mutated　NSCLC.　Two　sequences　of　peptides　(namely　P1　and　P2　peptide)　were　designed　for　synthesis　two　Au　clusters　(namely　P1-Au　and　P2-Au),　respectively.　These　two　clusters　specifically　target　the　extracellular　region　of　EGFR　and　enter　cancer　cells　through　endocytosis.　ICP-MS　measurements,　enzyme　activity　experiments　and　cytotoxicity　studies　in　H1650　cells　(exon　19　deletions　of　EGFR)　demonstrated　that　P1-Au　clusters　have　stronger　targeting　ability　towards　EGFR,　well　inhibits　EGFR　phosphorylation　and　outcome　a　better　anti-tumor　effect　than　that　of　P2-Au　clusters.　Further　experiments　revealed　that　the　P1-Au　clusters　enter　H1650　cells　through　the　clathrin-mediated　endocytosis　pathway,　escape　from　lysosomes　to　the　cytoplasm,　and　inhibit　the　phosphorylation　of　EGFR　exon　19　deletions　and　its　downstream　protein　to　induce　cancer　cell　apoptosis.　P1-Au　clusters　significantly　inhibited　the　tumor　growth　in　an　H1650　xenograft　model　via　suppress　EGFR　exon　19　deletions　mutant　activation.