Abstract The suicide rate has steadily increased in the United States during the past 2 decades. Cancer patients have elevated suicide risk because of prevalent psychological distress, treatment side effects, and potentially uncontrolled pain. Efforts to promote psychosocial and palliative care may reduce this risk. Using the 1999-2018 Multiple Cause of Death database, we found a decreasing trend of cancer-related suicide during the past 2 decades with an average annual percentage change (AAPC) of age-adjusted suicide rates of -2.8% (95% confidence interval [CI] = -3.5% to -2.1%) in contrast to an increasing trend of overall suicide rate (AAPC = 1.7%, 95% CI = 1.5% to 1.8%). We also observed the largest declines in cancer-related suicide rates among high-risk populations including male, older age, and certain cancer types, suggesting an evolving role of psycho-oncology and palliative and hospice care during this period.