Background: Health-related quality of life (HRQOL) is an important cancer care outcome. Patient-physician communication is linked to HRQOL, yet less is known about the role of other aspects of the patient-physician relationship in explaining HRQOL outcomes in cancer patients. Using secondary data from the Accountability for Cancer Care through Undoing Racism and Equity study, we examined associations between multiple patient-physician relationship factors and HRQOL in breast and lung cancer patients. Methods: The analysis included 283 patients receiving care at two cancer centers from 2013-2017. Survey data on socio-demographics, HRQOL, and patient-physician relationship (i.e., doctors’ respectfulness, time spent with doctors, doctors’ involvement of patient in decision-making, satisfaction with quality of care) were collected at baseline and during treatment. The primary outcome was a binary measure of poor-fair (vs. good-excellent) HRQOL 90 days post-diagnosis. We employed multivariate logistic regression to assess associations between patient-physician relationship factors and HRQOL. Results: In adjusted analyses, patients reporting high levels of physician respect had 78% lower odds of reporting poor-fair HRQOL than patients reporting low levels of respect (Adjusted Odds Ratio[AOR] = 0.22; 95%CI = 0.08-0.59). Patients who were optimally involved in their care had lower odds of poor-fair HRQOL than those less involved (AOR = 0.30; 95%CI = 0.12-0.77). Finally, patients who very satisfied with the quality of their care had a 40% lower odds of poor-fair HRQOL than those less satisfied with care (AOR = 0.40; 95% CI = 0.13-0.99). There was no association between amount of time spent with doctor and HRQOL. Conclusions: Multiple aspects of the patient-physician relationship, including doctor’s respectfulness, doctors’ involvement of patient in decision-making, and patient satisfaction with quality of care are associated with HRQOL among breast and lung cancer patients. Given the important role that HRQOL plays in treatment adherence and outcomes, these findings highlight the need for systems of care that optimize the physician-patient relationship in cancer care.