Objective To explore the effect of PKCι on maintaining the survival process of KRAS mutation colon cancer and its molecular mechanism.Methods HCT116 and RKO, colon cancer cells were selected and divided into blank control group, ATM group, shRNA-prkci group and shRNA-kras group. The apoptosis was determined by flow cytometry. Protein level and mRNA level were detected by western blot and qPCR. Cell location and relative expression of YAP1 were validated by immunofluorescence. Results In HCT116 cells carrying KRAS gene mutations, PKCι inhibition was accompanied by apoptosis and growth inhibition(P＜0.05). Furthermore, inhibition of PKCι significantly down-regulated YAP1 expression in HCT116. This effect was not obvious in RKO cells without KAS mutation. Conclusion PKCι maintains the survival of KRAS mutant colon cancer by regulating the expression of YAP1.PKCι and YAP1 are potential targets for colon cancer with KRAS mutation.