Epidermal growth factor receptor (EGFR) plays an important role in various types of cancer. However, the therapeutic agents that target EGFR have not produced favorable results in gastric cancer. miRNAs are known to regulate gene expression at the post-transcriptional level. We wondered if miRNAs could be potential therapeutic agents for the targeted therapy against EGFR. In this study, we found an increase in the copies of EGFR mRNA and the upregulated expression of the EGFR protein in gastric cancer tissues compared with normal gastric tissues. Both bioinformatic analysis and luciferase reporter assay revealed that miR-455 could directly bind with the 3'-untranslated region (3'UTR) of EGFR mRNA. Subsequently, in vitro studies were conducted to identify the effects of miR-455 on cell proliferation and migration and further confirm the cancer-promoting role of EGFR in gastric cancer. The results revealed that miR-455 negatively regulated EGFR expression at the post-transcriptional level, thus suppressing cell growth and migration. To conclude, our results offer a potential targeted therapeutic method against EGFR in gastric cancer mediated by miR-455.