The piRNA/PIWI system expression profile in the peripheral leukocytes of RA patients was discussed and verified for the first time in our project, and it was found that the piRNA/PIWI system was dysregulated and that two immunoregulation-related piRNAs, i.e., piR-hsa-27620 and piR-hsa-27124, had value as potential biomarkers to help improve the diagnostic ability of current indicators. Here, PIWIL1 is linked to rheumatoid arthritis.