BACKGROUND: Colony-stimulating factor 3 (CSF3) and its receptor (CSF3R) are known to promote gastric cancer (GC) growth and metastasis. However, their effects on the immune microenvironment remain unclear. Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2 (LILRB2) in GC. We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands, angiopoietin-like protein 2 (ANGPTL2) and human leukocyte antigen-G (HLA-G), contributing to immunosuppression. AIM: To investigate the relationship between CSF3/CSF3R and LILRB2, as well as its ligands ANGPTL2 and HLA-G, in GC. METHODS: Transcriptome sequencing data from The Cancer Genome Atlas were analyzed, stratifying patients by CSF3R expression. Differentially expressed genes and immune checkpoints were evaluated. Immunohistochemistry (IHC) was performed on GC tissues. Correlation analyses of CSF3R, LILRB2, ANGPTL2, and HLA-G were conducted using The Cancer Genome Atlas data and IHC results. GC cells were treated with CSF3, and expression levels of LILRB2, ANGPTL2, and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting. RESULTS: Among 122 upregulated genes in high CSF3R expression groups, LILRB2 showed the most significant increase. IHC results indicated high expression of LILRB2 (63.0%), ANGPTL2 (56.5%), and HLA-G (73.9%) in GC tissues. Strong positive correlations existed between CSF3R and LILRB2, ANGPTL2, and HLA-G mRNA levels ( CONCLUSION: The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands, with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.