Cancer is a devastating and debilitating chronic disease that affects both patients and their family members. There is evidence confirming that caring for relatives with chronic diseases by family members can be very challenging. Therefore, the aim of the present study was to predict caregiving burden based on cancer patient anxiety/depression and self-compassion in primary caregivers. This research falls within the category of descriptive-correlational studies. The statistical population of the study consisted of all cancer patients and their primary caregivers who had referred to Ayatollah Khansari Hospital in Arak. A sample size of 146 participants was determined based on correlation sample size calculations and selected through purposive sampling. The Caregiving Stress Questionnaire, Hospital Anxiety Depression Scale, and Reese Self-Compassion Questionnaire were used to collect data. The data were analyzed using SPSS through Pearson correlation coefficient and linear regression. The results showed that there is a positive and significant relationship between patient anxiety depression and caregivers' caregiving stress, and there is a negative relationship between caregiver self-compassion and caregiving stress. Based on these findings, the role of informal caregivers in promoting the health of chronically ill family members is recognized. Therefore, it is recommended that attention be given to the mental health of patients and the strengthening of protective factors in caregivers, in order to mitigate caregiving burden as a potentially erosive variable.