Gastric cancer (GC) is the most common and fast-growing malignancy of the digestive system, which has a high mortality. Chromobox homolog 2 (CBX2) has been reported to be highly expressed in cancer tissues compared with adjacent normal tissues. It has also been established that CBX2 is upregulated in GC cell lines by searching the Cancer Cell Line Encyclopedia. The aim of the present study was to investigate the biomolecular role and underlying mechanism of CBX2 in the proliferation, invasion and migration of GC cells. Short hairpin RNA-CBX2 and yes-associated protein (YAP) overexpression plasmids were constructed to regulate CBX2 and YAP expression, respectively. Additionally, the expression of certain mRNAs and proteins involved in the YAP/β-catenin pathway and those associated with cell invasion were assessed by western blotting and reverse transcription-quantitative PCR, respectively. The cellular behaviors of MFC cells were analyzed using Cell Counting Kit-8, colony formation wound-healing and Transwell assays. The results of the present study revealed that increased CBX2 expression was observed in GC cell lines compared with normal gastric cells. In addition, CBX2 knockdown inhibited the nuclear cytoplasm translocation of YAP, inducing its phosphorylation, and suppressing the activation of the β-catenin signaling pathway. The results also demonstrated that CBX2 depletion inhibited the proliferation, migration and invasion of GC cells by inactivating the YAP/β-catenin pathway. It was determined that CBX2 promoted the proliferation, invasion and migration of GC cells by activating the YAP/β-catenin pathway, suggesting that CBX2 is involved in the pathogenesis of GC and may represent a novel target for the clinical treatment of GC.