<p>Gastric cancer (GC) is a prevalent malignant tumor threatening human health. This study aimed to explore the potential mechanism of receptor-like tyrosine kinase (RYK) silencing-modified bone marrow-derived mesenchymal stem cells (BMSCs) in the progression of GC. BMSCs were transfected with the RYK siRNA and negative controls. Cell co-culture experiments were used to explore the interaction between different BMSCs and human gastric carcinoma cell line NCI-N87. Cancer cell proliferation, cell cycle, apoptosis, colony formative ability, and invasive ability were assessed. Western blot analysis was performed to determine the protein levels of cyclinA, Bcl-xL, Bcl-2, cleaved caspase 3, cleaved caspase 7, cleaved caspase 9, and cleaved PARP1 in NCI-N87 cells. Compared with NCI-N87 cells, co-culture of si-NC-modified BMSCs with NCI-N87 cells promoted the proliferation, colony formative ability, and invasion of NCI-N87 cells, inhibited the apoptosis of NCI-N87 cells, and reduced the proportion of NCI-N87 cells present in G2/M phase cells. In addition, compared with the si-NC-BMSCs + N87 group, the si-RYK-BMSCs + N87 group inhibited the proliferation, colony formative ability, and invasion of NCI-N87 cells, promoted the apoptosis of NCI-N87 cells, and increased the proportion of G2/M phase cells. Thus, RYK silencing-modified BMSCs can inhibit the proliferation, colony formative ability, and invasion of NCI-N87 cells, while inducing apoptosis and G2/M phase arrest.</p>