TheMIR663AHGgene encodes bothmiR663AHGandmiR663a. WhilemiR663acontributes to the defense of host cells against inflammation and inhibits colon cancer development, the biological function of lncRNAmiR663AHGhas not been previously reported. In this study, the subcellular localization of lncRNAmiR663AHGwas determined by RNA-FISH.miR663AHGandmiR663awere measured by qRT-PCR. The effects ofmiR663AHGon the growth and metastasis of colon cancer cells were investigated in vitro and in vivo. CRISPR/Cas9, RNA pulldown, and other biological assays were used to explore the underlying mechanism ofmiR663AHG. We found thatmiR663AHGwas mainly distributed in the nucleus of Caco2 and HCT116 cells and the cytoplasm of SW480 cells. The expression level ofmiR663AHGwas positively correlated with the level ofmiR663a(r= 0.179,P= 0.015) and significantly downregulated in colon cancer tissues relative to paired normal tissues from 119 patients (P< 0.008). Colon cancers with lowmiR663AHGexpression were associated with advanced pTNM stage (P= 0.021), lymph metastasis (P= 0.041), and shorter overall survival (hazard ratio = 2.026;P= 0.021). Experimentally,miR663AHGinhibited colon cancer cell proliferation, migration, and invasion. The growth of xenografts from RKO cells overexpressingmiR663AHGwas slower than that of xenografts from vector control cells in BALB/c nude mice (P= 0.007). Interestingly, either RNA-interfering or resveratrol-inducing expression changes ofmiR663AHGormiR663acan trigger negative feedback regulation of transcription of theMIR663AHGgene. Mechanistically,miR663AHGcould bind tomiR663aand its precursorpre-miR663a, and prevent the degradation ofmiR663atarget mRNAs. Disruption of the negative feedback by knockout of theMIR663AHGpromoter, exon-1, andpri-miR663A-coding sequence entirely blocked these effects ofmiR663AHG, which was restored in cells transfected withmiR663aexpression vector in rescue experiment. In conclusion,miR663AHGfunctions as a tumor suppressor that inhibits the development of colon cancer through itscis-binding tomiR663a/pre-miR663a. The cross talk betweenmiR663AHGandmiR663aexpression may play dominant roles in maintaining the functions ofmiR663AHGin colon cancer development.