Objective In this study, we aimed to examine the effect of post-traumatic growth and depressive symptoms on caregiver burden in caregivers of cancer patients. Methods This was a single-center cross-sectional observational descriptive study conducted at a medical oncology clinic. The study included 214 caregivers of cancer patients. Participants were assessed with a sociodemographic information form, the Turkish versions of the Zarit Caregiver Burden Scale (ZCBS), the Posttraumatic Growth Inventory (PTGI), and the Beck Depression Inventory (BDI). Results The mean ZCBS, PTGI, and BDI scores were 42.7 ±13.8, 67.8 ±22.3, and 13.5 ±9.8, respectively. There was a negative correlation (r=-0.407, p<0.001) between the ZCBS and the PTGI total scores, a positive correlation (r=0.636, p<0.001) between the ZCBS total and BDI scores, and a negative correlation (r=-0.426, p<0.001) between the PTGI total and BDI scores. Age, gender, income level, and history of psychiatric treatment were not independent predictive factors for the ZCBS total scores. PTGI total score (B=-0.107, 95% CI: -0.178 to -0.037, p=0.003) and BDI score (B=0.776, 95% CI: 0.602-0.950, p<0.001) were independent predictive factors for ZCBS total scores. Conclusions Our study revealed a significant negative relationship between caregiver burden and PTGI in caregivers of metastatic cancer patients, and it was found that depression negatively affects burden in caregivers. Posttraumatic growth can be a protective buffer against the burden of care and depression among caregivers.