Purpose <p>The purpose of this study was to explore caregiver burden and its influencing factors in cancer patients undergoing palliative PTBD from both caregiver and patient perspectives.</p> Methods <p>A cross-sectional study was conducted on caregiver-patient dyads who underwent palliative percutaneous transhepatic biliary drainage (PTBD) from January to December 2023 at a tertiary hospital in western China. The Zarit Caregiver Burden Interview (ZBI), the Chinese version of the Family Resilience Assessment Scale (FRAS), the Self-Perceived Burden Scale (SPBS), and the Hospital Anxiety and Depression Scale (HADS) were used to assess outcome variables. Sociodemographic data and PTBD-related characteristics were also collected. Multiple linear regression was conducted to identify the influencing factors of caregiver burden.</p> Results <p>A total of 185 caregiver-patient dyads were included in this study. The participants had a mean age of 51.6&#xa0;years, and 68.6% were female. The median ZBI score was 58.7, with 47.5% of caregivers experiencing severe burden. Caregivers' daily time spent on caregiving, anxiety (β = 1.20, <i>p</i> = 0.001), depression (β = 0.86, <i>p</i> = 0.009), and family resilience (β = -0.11, <i>p</i> = 0.016) were found to be influencing factors of caregiver burden. Additionally, patient age (β = 0.20, <i>p</i> &lt; 0.001), female sex (β = 3.61, <i>p</i> = 0.010), having more than one tube (β = 4.22, <i>p</i> = 0.003), and the tube maintenance institution were identified as influencing factors of caregiver burden.</p> Conclusion <p>Caregivers of cancer patients undergoing palliative PTBD had a considerable burden, which was influenced by factors from both the caregiver and patient perspectives. It is imperative for healthcare providers to develop interventions that target the modifiable influencing factors identified to support these caregivers effectively.</p>