SIRT6 (sirtuin 6) has been identified as an anti-aging protein, and SIRT6-deficient mice display numerous progeroid and aging-like phenotypes. However, there are no reports correlating skin aging with SIRT6. To explore how SIRT6 affects collagen metabolism and determine its role in skin aging, the levels of COL1A1 (type I collagen), COL3A1 (type III collagen) and TGFβ1 (transforming growth factor β1) mRNA expression were detected by RT-Q-PCR (real-time quantitative PCR), and MMP1 (matrix metalloproteinase 1) concentration in HDF (human dermal fibroblast) supernatants was determined by ELISA after blocking SIRT6 using siRNA (small interefering RNA). Compared with the control group, blocking SIRT6 significantly decreased the HC (hydroxyproline content). SIRT6 knockdown in HDFs inhibited the transcription of COL1A1 and prompted MMP1 secretion, but had no effect on COL3A1 and TGFβ1. Furthermore, NF-κB p65 (nuclear factor κB p65) protein in the nucleus was increased after blocking SIRT6. The results suggest that SIRT6 knockdown in HDFs influence the synthesis and degradation of collagen by hyperactive NF-κB signalling, which leads to a decrease in dermal collagen fibrils. SIRT6 may therefore play an important role in the process of skin anti-aging.