A time-dependent risk informed integrated safety assessment methodology is suggested to evaluate the response of nuclear power plants under complex accident sequences caused by failures of multiple safety features. Event propagation is modeled based on the combination of deterministic and probabilistic safety assessment methods, with results representing changes in plant risk over time. Operators can utilize the time-dependent risk information as a quantitative basis, and results can determine the degree of safety enhancement by the improvement of emergency operator action procedures or by strengthening the design of safety features. The concepts of consequential failure probability and point-estimate failure time are introduced. The consequential failure probability, calculated from central limit theorem, identifies the key safety system and provides a precise risk calculation. The point-estimate failure time, using non-parametric order statistics, justifies the crediting of emergency operator actions. As a case study, risk of large early radioactive release due to pressure-induced multiple steam generator tube rupture following main steam line break accident in Advanced Power Reactor 1400 is considered. Results are used to discuss the credibility of operator mitigation actions, and a remedy to enhance plant safety to satisfy safety goals is suggested.