Let \(\mathcal {G}\) be a generalized matrix algebra. A linear map \(\varphi : \mathcal {G} \rightarrow \mathcal {G}\) is said to be an anti-derivation at zero if \(T\varphi (S)+\varphi (T)S=0\) for every \(S, T \in \mathcal {G}\) with \(ST=0\) . In this paper, we describe the general form of \(\varphi \) and consider the question of when \(\varphi \) equals to zero. The results are then applied to full matrix algebras and some operator algebras.