De Quervain's disease is a stenosing tenosynovitis of the first dorsal compartment of the wrist. Histopathological studies have reported that the thickening of the first dorsal retinaculum is characterized by degeneration rather than inflammation. However, significant infiltration of mast cells and macrophages was noted in a torn tendon study, which suggested that innate immune pathways are part of the mechanism that mediates early tendinopathy. Recently, Interleukin-20 (IL-20) has been reported to provoke potent inflammation and regulate angiogenesis and chemotaxis, which are important for the pathogenesis of inflammatory diseases. The main purpose of our study was to investigate the correlation between IL-20 and tumor necrosis factor (TNF-α) and clarify the potential predictor of tendinopathy progression. Hematoxylin and eosin (H & E) and immunohistochemistry (IHC) staining were used to score and analyze the clinical outcome. TNF-α, IL-20 and related inflammation cytokines were examined. Moreover, the tenocytes were cultured with a stimulator and were used to examine inflammatory cytokine secretions. A real-time polymerase chain reaction (Real-time PCR) was used to detect the gene expression profile. The IHC data showed that TNF-α is up-regulated in grade III de Quervain's. The analysis data showed that IL-20 is positively correlated with TNF-α and disease severity. The real-time PCR showed that the inflammation stimulator enhanced the expression of IL-20 mRNA expression. Inflammation cytokines such as TNF-alpha, transforming growth factor-β (TGF-β) and IL-1 have been used as predictors of de Quervain's; IL-20 is a new predictor based on this study. In the future, IL-20 expression's involvement in the molecular mechanism of the severity of de Quervain's should be further investigated.