Tobacco smoke is known to be an element contributing to accelerate premature skin ageing. Cysteine-rich 61 (Cyr61) is a member of the connective tissue factor CCN (Cyr61, CTGF and Nov) family, and early growth response-1 (Egr-1) is a generally expressed member of the zinc-finger family of transcription factors. To investigate the regulatory potential of Egr-1 on expression of Cyr61 by smoking, this study examined the hypothesis that cigarette smoke-induced Egr-1 induces expression of Cyr61 in human skin dermal fibroblasts (HSDF). HSDF were exposed to different concentrations of cigarette smoke extract (CSE) for 24 h; a cytotoxicity assay was then performed for the detection of cell proliferation. Results of Western blot and reverse transcription-polymerase chain reaction (RT-PCR) showed that CSE induces a transient synthesis of Egr-1 in HSDF. Cyr61 mRNA and protein levels showed a marked increase in a time-dependent manner after CSE exposure. Following transfection with an Egr-1 overexpression vector, HSDF showed increased activity of the Cyr61 promoter in a dose-dependent manner. Using Egr-1 interfering RNA, we confirmed that CSE-induced Cyr61 expression was dependent on Egr-1 expression. Findings of this study indicate that Egr-1-dependent induction of Cyr61 may contribute to premature skin ageing by smoking.