Transposable elements (TEs) are DNA elements that can change their position within or between chromosomes. Most active TEs are retrotransposons, which transpose through a RNA intermediate. Since retrotransposons comprise high proportions in cell genomes, their frequent transposition may cause deleterious effects on the structure and function of the host cell genomes, thus causing serious genetic diseases such as cancer. Host cells therefore developed defense strategies to restrict these mobile elements. piRNA, which belongs to non-coding interfering RNAs, can efficiently decrease the level of retrotransposon RNA intermediates at transcriptional or post-transcriptional stages. In this review, we summarize the progress in mechanisms of piRNA-mediated retrotransposon inhibition. We hope that this review may shed light on the research of transposon and genome regulation.