High cell uptake owing to the exosome fused with HER2 proteins, efficient synergic effect in cell killing compared to single drug. Exosomes’ loading capacity (LC) for 5-FU and miR-21i was around 3.1% and 0.5%, respectively. THLG-EXO penetrated Her2-mcherry-SGC-7901 cells more efficiently than SGC-7901 WT, and a significant reduction in tumor volume was seen in the group treated with the THLG-EXO/5FU/miR-21i compared to the THLG-EXO and THLG-EXO/5FU groups. This evidence concerns the gene ERBB2 and neoplasm.