Abstract In plants, post-transcriptional gene silencing (PTGS) tightly regulates development, maintains genome stability and protects plant against foreign genes. PTGS can be triggered by virus infection, transgene, and endogenous transcript, thus commonly serves as an RNA-based immune mechanism. Accordingly, based on the initiating factors, PTGS can be divided into viral-PTGS, transgene-PTGS, and endo-gene-PTGS. Unlike the intensely expressed invading transgenes and viral genes that frequently undergo PTGS, most endogenous genes do not trigger PTGS, except for a few that can produce endogenous small RNAs (sRNAs), including microRNA (miRNA) and small interfering RNA (siRNA). Different lengths of miRNA and siRNA, mainly 21-, 22- or 24-nucleotides (nt) exert diverse functions, ranging from target mRNA degradation, translational inhibition, or DNA methylation and chromatin modifications. The abundant 21-nt miRNA or siRNA, processed by RNase-III enzyme DICER-LIKE 1 (DCL1) and DCL4, respectively, have been well studied in the PTGS pathways. By contrast, the scarceness of endogenous 22-nt sRNAs that are primarily processed by DCL2 limits their research, although a few encouraging studies have been reported recently. Therefore, we review here our current understanding of diverse PTGS pathways triggered by a variety of sRNAs and summarize the distinct features of the 22-nt sRNA mediated PTGS.