Flood events impose great distress on chemical industrial areas, since they may cause Natech accidents involving multiple units. Furthermore, escalation vectors exerted by major accidents can trigger knock-on events, so-called domino effects, causing very severe consequences. In the present study, a methodology is proposed to include domino effects triggered by floods in a quantitative risk assessment, by addressing the frequency assessment of flood-induced domino scenarios. A comprehensive procedure is developed, combining the fragility model for unit damage due to floods, probability estimation for domino escalation, and combinatorial analysis for overall scenarios. Moreover, the flow interference due to the layout of chemical industrial areas is explored to calculate the damage probability more accurately. The methodology has been demonstrated by a case study, the changes in risk indexes and damage zones due to Natech domino effects are discussed. The results show that the overall risk significantly increases with respect to conventional scenarios when considering flood-induced Natech events and domino effects, evidencing the importance of risk analysis of Natech-related domino effects. Finally, some prevention measures have been proposed for chemical industrial areas to make them more resilient and safer when it comes to floods. (C) 2021 Published by Elsevier B.V. on behalf of Institution of Chemical Engineers.