Objective To explore the effects of long non-coding RNA(lncRNA) small nucleolar RNA host gene 16(SNHG16) knockdown on the apoptosis of gastric cancer AGS cells and its possible mechanism. Methods Well-cultured gastric cancer AGS cells in the third generation was randomly divided into three groups: the blank control group, negative control group, and si-SNHG16 group. Blank medium, medium with negative control si-NC and medium with interference si-SNHG16 were added into the blank control group, negative control group, and si-SNHG16 group, respectively. After transfection with si-SNHG16 for 48 h in the gastric cancer AGS cells, the interference efficiency of SNHG16 and the expression of p53 gene after SNHG16 knockdown were detected by qRT-PCR assay. The apoptosis was determined by Annexin V-FITC/PI double staining flow cytometry and Hoechst 33342 staining. The expression of p53, Bcl-2, Bax and Cleaved Caspase-3 protein was evaluated by Western blotting. The activity of Caspase-3 enzyme was detected by spectrophotometry assay. Results At 48 h after transfection, compared with the blank control group and negative control group, the relative expression of lncRNA SNHG16 decreased, and the relative expression of p53 gene increased in the si-SNHG16 group(both P<0.05). Besides, the apoptosis rate and apoptotic cells of the si-SNHG 16 group all increased(all P<0.05). The expression of p53 protein and apoptosis-related proteins(Bax and Cleaved caspase-3) were up-regulated significantly(all P<0.05), but the expression of Bcl-2 was down-regulated(P<0.05). Moreover, the activity of Caspase-3 enzyme was enhanced(P<0.05). No significant difference was found in the above parameters between the blank control group and negative control group(all P>0.05).Conclusion LncRNA SNHG16 knockdown could promote the apoptosis of gastric cancer AGS cells by activating the p53 signaling pathway downstream apoptosis-related protein expression and thus initiating the apoptosis. [ABSTRACT FROM AUTHOR]