Hybrid imaging methods combining diffuse optical tomography (DOT) and other anatomical or nonoptical functional modalities have been widely investigated to improve imaging performance degraded by the strong optical scattering of biological tissues, through constraining the reconstruction process by prior structures. However, these modalities with different contrast mechanisms may be ineffective in revealing early-staged lesions with high optical contrast but no morphological changes. Photoacoustic tomography (PAT) is particularly useful for visualizing light-absorbing structures embedded in soft tissues with high spatial resolution. Although it is still challenging for PAT to quantitatively disclose the absorption distribution, the modality does provide reliable and specific a priori information differentiating light-absorbing structures of soft tissues and might be more appropriate to guide DOT in lesion diagnosis, as compared with other anatomical or nonoptical functional modalities. In this study, a PAT-guided DOT approach is introduced with both soft- and hard-prior regularizations. The methodology is experimentally validated on small-animal-sized phantoms using a computed-tomography-analogous (CT-analogous) PAT/DOT dual-modality system, focusing on future whole-body applications. The results show that the proposed scheme is capable of effectively improving the quantitative accuracy and spatial resolution of DOT reconstruction.