Previous Face Anti-spoofing (FAS) works face the challenge of generalizing in unseen domains. One of the major problems is that most existing FAS datasets are relatively small and lack data diversity. However, we find that there are numerous real faces that can be easily achieved under various conditions, which are neglected by previous FAS works. In this paper, we conduct an Anomalous cue Guided FAS (AG-FAS) method, which leverages real faces for improving model generalization via a De-spoofing Face Generator (DFG). Specifically, the DFG trained only on the real faces gains the knowledge of what a real face should be like and can generate a "real" version of the face corresponding to any given input face. The difference between the generated "real" face and the input face can provide an anomalous cue for the downstream FAS task. We then propose an Anomalous cue Guided FAS feature extraction Network (AG-Net) to further improve the FAS feature generalization via a cross-attention transformer. Extensive experiments on a total of nine public datasets show our method achieves state-of-the-art results under cross-domain evaluations with unseen scenarios and unknown presentation attacks.