Oxidative stress is one of the most important causes of the cellular senescence process. Previous studies showed that beta-catenin can regulate FoxO3a and this association was enhanced in cells exposed to oxidative stress. It has also been reported that beta-catenin can regulate some senescence-related proteins. We propose that beta-catenin may play a crucial role in senescence of normal human primary skin fibroblasts (NHSFs). Here, we explored the roles and mechanisms of beta-catenin on H(2)O(2)-induced senescence in NHSFs. beta-catenin expression was decreased in NHSFs after H(2)O(2) treatment. Overexpression of beta-catenin in NHSFs led to a marked delay of many senescent phenotypes induced by H(2)O(2). Furthermore, overexpression of beta-catenin in NHSFs can antagonise the alteration of reactive oxygen species accumulation and some senescence-related proteins expression induced by H(2)O(2) treatment. Our data demonstrated that beta-catenin can protect NHSFs from H(2)O(2)-induced premature senescence by alleviating oxidative stress and regulating some senescence-related molecules.