The application of photo-Fenton process is restricted by the acidic pH and additional hydrogen peroxide (H2O2). In order to overcome these drawbacks, a photo-Fenton system of CdS/rGO/Fe2+ which can perform at natural pH with in situ-generated H2O2 has been successfully developed. Highly efficient photo-Fenton degradation of phenol was achieved under the visible light irradiation via the CdS/rGO/Fe2+ system. Experimental results showed that phenol could be degraded completely in 1 h at natural pH. The plentiful in situ generation of H2O2 was further proved to act as an important role in phenol degradation with the addition of Fe2+. The advantages of degradation at natural pH with in situ-generated H2O2 can provide a new prospective to the environmental-friendly Fenton process.