Morphine is commonly used in clinical management to alleviate moderate-to-severe pain. However, prolonged and repeated use of morphine leads to tolerance. Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. The mechanisms underlying morphine tolerance are still not completely understood. MicroRNAs (miRNAs) are small noncoding RNAs containing 18~22 nucleotides that modulate gene expression in a post-transcriptional manner, and their dysregulation causes various diseases. miRNAs bind to the 3ʹ-UTR (untranslated region) of target gene mRNA, inhibiting or destabilizing translation of the transcripts. Morphine causes differential miRNA upregulation or downregulation. This review will present evidence for the contribution of miRNAs to tolerance of the antinociception effect of opioids.