Colon　cancer　is　a　common　malignancy,　and　its　morbidity　and　mortality　have　been　increasing　in　recent　years　in　China.　Shikonin　(Shi),　a　naturally　occurring　naphthoquinone,　exhibits　anticancer　activity.　However,　the　mechanisms　of　action　of　Shi　remain　unclear.　The　aim　of　the　present　study　was　to　investigate　the　antitumor　mechanism　of　Shi　in　colon　cancer　cells.　The　effects　of　different　Shi　concentrations　on　the　viability　of　colon　cancer　cells　using　MTT,　colony　formation　and　wound-healing　assays　were　assessed.　Western　blot　analysis　was　performed　to　detect　the　expression　of　LC3-II,　p62.　Shi　effectively　suppressed　viability　and　cell　migration,　and　induced　autophagy　in　colon　cancer　cells.　Yes-associated　protein　(YAP)　increases　cell　viability,　and　inhibits　cell　apoptosis　and　cell　contact.　Expression　of　YAP　is　downregulated　by　Shi.　The　cytotoxic　effects　of　Shi　were　further　investigated　on　YAP　overexpression　and　on　YAP　knockout　cell　lines.　The　findings　revealed　that　Shi　suppressed　the　viability　and　induced　autophagy　of　colon　cancer　cells.　Additionally,　YAP　expression　reversed　the　effects　of　Shi.　The　results　of　the　present　study　suggest　that　Shi　may　be　a　promising　anticancer　treatment　for　colon　cancer,　and　YAP　may　be　a　potential　diagnostic　marker　for　colon　cancer.