OBJECTIVE: The aim of this study was to explore the moderated mediation mechanism of the relationships among perceived stress, psychological distress, experiential avoidance and trait mindfulness of hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE) in China. METHODS: This study utilized a cross-sectional approach to gather data from 458 HCC patients undergoing TACE. Participants completed self-report measures assessing psychological distress, perceived stress, experiential avoidance and trait mindfulness. Mediation and moderation analyses are carried out in SPSS macro PROCESS. RESULTS: Perceived stress could affect psychological distress and experiential avoidance could mediate this relationship (mediation effect = 0.041, [95%CI=(0.027, 0.056)]). Trait mindfulness played a role as a moderator in the direct and indirect effect of perceived stress on psychological distress. CONCLUSION: Our findings underscore the vital role of experiential avoidance and trait mindfulness to relieve psychological distress, and provide practical implications for mental health intervention programs of HCC patients undergoing TACE.