The hospitality industry is particularly vulnerable to human trafficking crimes. Unfortunately, prior research has not sufficiently tackled this important issue. This study investigates hotel employees’ motivation and engagement in anti-human-trafficking initiatives by conducting in-depth qualitative interviews. A total of 28 hotel professionals, ranging from managers to frontline staff members, who work at both international chains and independent hotel properties, participated in the investigation. Data were analyzed using the MAXQDA Pro 12 package. Results identified five main themes (leadership, organizational system, peer support, technology, and training) consisting of 21 factors that impact hotel employees’ engagement in anti-human-trafficking initiatives. The study findings are valuable to hotel practitioners, policymakers, and society at large in order to help prevent human trafficking crimes.