PiRNAs are a small class of non-coding small RNAs newly discovered in recent years. Millions of piRNAs have been discovered to date, and more than 20,000 piRNA genes have been found in the human genome. Due to the relatively small number of studies related to piRNA, our understanding of piRNAs is very limited. Currently, the clear biological function of piRNAs is transposon mobilization inhibition by promoting transcript degradation and regulating chromatin formation. In addition, piRNAs can form piRNA-PIWI protein complexes with some members of the PIWI branch of the Argonaute protein. Based on these biological functions, piRNAs and PIWI proteins are important in maintaining the genomic integrity of germline cells. Because of this, the popularity of piRNAs research has been focused on its role in germline cells for a long time after the discovery of piRNAs. As the field of research expands, there is growing evidence that piRNAs and PIWI proteins are abnormally expressed in various types of cancers, which may be potential cancer biomarkers and cancer therapeutic targets. In this review, we will focus on the relationship between piRNAs and PIWI proteins and cancers based on previous research, as well as their significance in cancer detection, grading and treatment.