Colorectal cancer (CRC) is one of the most common cancers worldwide with a high incidence and mortality. Although many treatment options are available in stage IV disease, the clinical outcome is still minimal. The primary treatment problem in metastatic colorectal cancer (mCRC) is early liver metastases that occur in more than 50% of patients. First-line treatment in metastatic colorectal cancer (mCRC) is a combination of chemotherapy plus targeted therapies like Cetuximab or Bevacizumab depending on K-RAS status. The decision of which regimen to choose is difficult because almost half of the patients don't receive second-line treatment due to complications or death. To avoid exposing non-responding patients to inefficient and harmful therapies new robust biomarkers are needed. Ongoing studies have demonstrated constantly that microRNAs (miRNAs) could become suitable biomarkers for screening and treatment response. In CRC, miR-31-3p and miR-31-5p dysregulation seems to have a particular role in evaluating treatment response from anti-EGFR therapy. In this review, we will present up to date information on the role of miRNA-31-3p and miR-31-5p in CRC with a particular focus in treatment response of metastatic K-RAS wild-type CRC treated with anti-EGFR molecules.