Objective To investigate the effect of long non-coding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) on the proliferation, apoptosis, migration, and invasion of colorectal cancer (CRC) cells via the miR-106b-5p/ PHD family finger protein 1 (PHF1) axis. Methods The expression of SNHG16, miR-106b-5p, and PHF1 in CRC tissues, adjacent normal tissues, CRC cell lines (LoVo, Caco-2, HCT116 and SW480), and normal human colon epithelial cells (CCD 841 CON) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). SW480 cells were randomly divided into Control group, si-NC group, si-SNHG16 group, si-SNHG16+inhibitor-NC group, si-SNHG16+ miR-106b-5p inhibitor group, si-PHF1 group, miR-NC group, miR-106b-5p group, miR-106b-5p + pcDNA group, and miR-106b-5p+pcDNA-PHF1 group. The expression levels of SNHG16, miR-106b-5p, and PHF1 in SW480 cells were detected by qRT-PCR. The proliferation, apoptosis, migration, and invasion abilities of SW480 cells were detected by MTT method, flow cytometry and Transwell method, respectively. The interactions between SNHG16, miR-106b-5p, and PHF1 were verified by dual luciferase reporter gene experiments. The protein level of PHF1 was measured by Western blot. Results SNHG16 and PHF1 were expressed at high levels, while miR-106b-5p was expressed at low levels(P<0. 05), in CRC tissues and cells. SW480 cells with the highest expression of SNHG16 were selected for a transfection experiment. The down-regulation of SNHG16 reduced the proliferation, migration, and invasion and promoted the apoptosis of SW480 cells (P<0. 05). MiR-106b-5p was able to interact with SNHG16, and its inhibitor restored the inhibitory effect of silencing SNHG16 on SW480 cell progression (P<0. 05). PHF1 was a target of miR-106b-5p, and silencing PHF1 inhibited the progression of SW480 cells (P<0. 05). PHF1 overexpression restored the inhibitory effect of miR-106b-5p on CRC cell progression (P<0. 05). SNHG16 promoted the expression of PHF1 in SW480 cells by downregulating miR-106b-5p (P<0. 05). Conclusions LncRNA SNHG16 regulates miR-106b-5p/ PHF1 axis by targeting to promote the proliferation, migration, and invasion of CRC cells and inhibits apoptosis.