Background <p>This study examines the dynamic changes between cultural worldview and self-esteem as distal defense mechanisms in cancer patients and explores the role of these mechanisms in the different psychological stages of cancer patients’ resistance to death, thereby elucidating the unique responses of cancer patients to the salience of death.</p> Methods <p>Our sample comprises 113 cancer patients and 92 dental pain patients. We measured participants’ levels of cultural worldview defenses, death thought accessibility (DTA), self-esteem, depression, and suicidal ideation in two studies.</p> Results <p>In Study 1, increased levels of cultural worldview defenses coincided with increased levels of DTA. Initial avoidance and denial inhibited cultural worldview defenses in cancer patients, which were progressively strengthened in subsequent psychological stages of death. In Study 2, there were no significant differences in explicit self-esteem among cancer patients in different psychological stages of death; however, there were differences in tests of implicit self-esteem, with the lowest scores on the depression and suicidal ideation scales in the Acceptance of Death stage, the most pronounced suicidal ideation in the Bargaining stage, and the highest scores on depression in the Avoidance of Death stage.</p> Conclusion <p>The findings of the study indicate that cancer patients exhibited dynamic shifts in their cultural worldviews and self-esteem during the psychological phases of death. Interestingly, self-esteem may be a more effective defense mechanism than cultural worldview in this context.</p>