Background/Aim: Sunitinib is a tyrosine kinase inhibitor routinely used as first-line therapy in metastatic renal cell carcinoma (mRCC). Emerging evidence suggests that microRNAs (miRNAs) could be suitable biomarkers with predictive potential in mRCC. The aim of this study was to identify miRNA-based predictive biomarkers of therapy response to avoid unnecessary therapy to non-responding patients. Patients and Methods: High-throughput miRNA microarray profiling was performed on a cohort of 47 patients treated with sunitinib. Validation of candidate miRNAs was carried out on an independent cohort of 132 mRCC patients using qRT-PCR. Results: Out of 158 miRNAs (65 down-regulated, 93 up-regulated), six miRNAs were chosen for independent validation and miR-376b-3p was confirmed to be differentially expressed in tumors of patients with primary resistance versus long-term response (p<0.0002). Conclusion: A predictive miRNA associated with progression free survival in metastatic renal cell carcinoma patients treated with sunitinib was identified.