Background: Placental growth factor is involved in human gastric cancer initiation and progression through stimulating the proliferation, angiogenesis, invasion and metastasis of cancerous cells. Previous studies indicate that the expression profiles of hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 change in MKN-45- derived gastric cancer stem-like cells. Therefore, this study aims to investigate the effect of PlGF knockdown on hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 expressions in MKN-45-derived gastric cancer stem-like cells.Methods: We used a non-adhesive culture system to derive the cancer stem-like cells from MKN-45 cells. PlGF gene silencing was performed by PlGF-specific siRNA. The transcript of PlGF and miRNAs were measured by real-time RT-PCR. We conducted bioinformatics analyses with the online software programs TargetScan, miRanda, miRWalk, PicTar, and the Database for Annotation, Visualization, and Integrated Discovery tools to predict miRNAs’ targets and their signaling pathways.Results: hsa-let-7b-3p had a 2.28-fold up-regulation, whereas we observed downregulation of hsa-mir-451b (25%), hsa-mir-4290 (34%), and hsa-mir-22-3p (9%). Bioinformatics analysis results indicated that the miRNA target genes TGF-β, MAPK, and Wnt, and hedgehog signaling pathways contributed to cancer initiation and progression by influencing different cellular behaviors.Conclusion: We suggest that PlGF signaling may influence miRNA expression profiles in MKN-45-derived cancer stem-like cells, which can influence the expressions of different genes and signaling pathways. However, more empirical studies should determine the exact effect of PlGF knockdown on the expression of miRNA targets in cancer stem-like cells to locate their actual gene targets.