Public e-participation has become the main form of triggering policy agenda setting. Accordingly, revealing the key factors and internal mechanism of a triggering process is conducive to improving the theoretical system of policy agenda setting. This study uses the public e-participation perspective to (1) construct an analysis framework of policy agenda setting based on theory of multiple streams, (2) introduce 40 events from 2015 to 2019, and (3) conduct qualitative comparative analysis to analyze the trigger factors and paths of policy agenda setting. The setting of policy agenda triggered by public e-participation is the result of interaction among social issues, participants, and policy outputs. Formation of public opinion pressure is the main trigger of policy agenda setting; participation of the public, opinion leaders, and media has a positive impact on policy agenda setting; and implementation of policy output plays a decisive role in implementing policy agenda setting. Three types of typical trigger paths can be summarized: (1) from “event-driven” to “government response” of event-driven participation, (2) from “public interaction” to “reaching consensus” of public interaction participation, and (3) from “public issues” to “policy outputs” of public opinion output participation. These paths reflect the main mechanism of e-participation that triggers policy agenda setting.