Colorectal cancer (CRC) is the most diagnosed cancer with the highest mortality rate each year globally. Although there are treatments for CRC, the development of resistance to therapies decreases the success of treatments. In vitro studies using the Caco-2 cell line have revealed the anticancer properties of silver nanoparticles (AgNPs) as a possible treatment for this disease. This study considered four researches that evaluated the proteomic profiles of cells of the Caco-2 line exposed to AgNPs. We performed a bioinformatics analysis to predict protein-protein interaction, hub genes, Gene Ontology (molecular function, biological process, and cellular components), KEGG pathways, analysis of expression, and immune cell infiltration. For these analyses, the STRING, DAVID, UALCAN, GEPIA2, and TISIDB databases were used. The results in Gene Ontology show that AgNPs cause a deregulation of genes related to cell-cell adhesion, the cytoplasm, the centriole, and carbon metabolism. Hub genes were identified, including GADPH, ENO1, EEF2, and ATP5A1, which showed differential expression in patients with adenocarcinoma of the colon and rectum. Additionally, the expression of the hub genes and immune cells was correlated. It was found that ATP5A1 and ENO1 were positively correlated with the infiltration of CD4+ T lymphocytes in colon adenocarcinoma and a negative correlation between GADPH and PDIA3 with the infiltration of NK cells and CD4+ T lymphocytes in rectal adenocarcinoma, respectively. In conclusion, the administration of AgNPs causes an alteration of biological processes, cellular components, metabolic pathways, deregulation of hub genes, and the activity of immune cells leading to a potential anticancer effect.