Work zone traffic safety under adverse weather conditions has been a serious concern for drivers and transportation agencies. Existing studies on work zone traffic safety with statistical approaches are limited by the availability of data from historical crashes. To date, there is no comprehensive simulation framework to assess work zone traffic safety under adverse driving environments by considering both multi-vehicle and single-vehicle crashes. To fill this gap, this paper presents an integrated framework to evaluate traffic safety in work zone under adverse driving conditions by considering specific work zone configuration, weather and road surface conditions. A new risk index is introduced to assess the traffic safety risk of work zones by integrating the risks of multi-vehicle crashes and single-vehicle crashes. Traffic safety of a typical work zone under different weather conditions is studied to demonstrate the proposed framework. The impacts of the differential speed limits (DSL) and truck proportion on the work zone traffic safety are also investigated. Results show that adverse weather may increase the crash risk in work zones. The effect of DSL on the work zone traffic safety is found to be insignificant while the truck ratio influences the work zone safety in the rainy and snowy weather by primarily affecting the multi-vehicle crash risks.