Objective To investigate the targeting of transforming growth factor β1 (TGF-β1) expression by Ranbinding protein 9 (RANBP9) and its effect on colorectal cancer Colo320 cell apoptosis. Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database. The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments. Colo320 cells were transfected with pcDNA3. 1-GFP-RANBP9 and control pcDNA3. 1-GFPRANBP9-NC plasmids, respectively, and normal control cells were established without transfection. The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry, the mitochondrial membrane potential was detected by JC-1 staining, and RANBP9 and TGF-β1 protein expression were detected by Western blot. Results RANBP9 expression was significantly reduced in colon cancer tissues. Compared with patients with low RANBP9 expression, patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue. Compared with patients with high TGF-β1 expression, patients with low TGF-β1 expression had a significantly higher survival curve (P<0. 05). RANBP9 targeted the expression of TGF-β1 in colon cancer. Compared with the normal group, cell growth, mitochondrial membrane potential, and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group (P<0. 05). Conclusions RANBP9 can target the expression of TGF-β1, promote the growth of Colo320 colon cancer cells, decrease the mitochondrial membrane potential, and induce apoptosis.