Under normal operation condition of nuclear power plants, there may exist some special phenomena related to high burnup fuel cladding, such as breakaway oxidation, inner surface oxygen ingress and hydrogen pickup embrittlement. The effects of these phenomena on cladding fracture limit during LOCA conditions were investigated by fuel cladding research program sponsored by U.S. NRC. Based on the research, new LOCA acceptance criterion 10CFR50.46c draft was agreed and released. In the present study, research on compliance between large break LOCA of HPR1000 and new LOCA acceptance criterion 10CFR50.46c was performed. Firstly, a hydrogen content prediction model for different cladding material was innovatively proposed and then large break LOCA analysis of HPR1000 at different burnup points was performed. Research showed that the analysis results of large break LOCA of HPR1000 could meet requirement of 10CFR50.46c. The PCT and transient ECR margin were 190.1 °C and 10.1% respectively which were large enough for large break LOCA to ensure reactor core safety.