Integrated system validation (ISV) is an important part of Human Factors Engineering Review of a nuclear power plant (NPP) employed to evaluate whether the design of function systems of NPPs support safe operations of operators. Workload evaluation of NPPs operators for ISV remains a problem due to a lack of objective indices and low creditability of subjective ratings. This study aims to establish one workload evaluation model based on physiological and activity indices. An ISV experiment of digitalized main control room was conducted on Yangjiang NPP Full-Scope Simulator. A task scenario of Diverse Human Interface Panel (DHP) and Severe Accident Panel (SAP) was selected from real NPPs task scenarios. Four operators participated in this experiment and finished the task scenario. Physiological and activity data were collected during the experiment and 14 indices were calculated. Task complexity were analyzed using VACP (Visual, Auditory, Cognitive and Psychomotor) theory. The result correlation analysis between task complexity and physiological & activity indices showed a significant positive relation with all p-value < 0.05. Finally, a workload evaluation model is constructed. This model can be used in ISV to evaluate the task complexity and workload during human reliability analysis based on the physiological response of NPPs operators.