Abstract Background: The concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. The aim of this study was to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients. Methods: This cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions by using bivariable logistic regression models and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16. Results: Of 262 patients who used herbal medicines, 209 patients [79.8% (95% CI: 75.2 – 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n=163, 78%), and minor and moderate herb-drug interactions were caused by green tea (n=34, 16.3%) and peppermint (n=78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43–2.58; P-value<0.0001) and the experience of pain during chemotherapy courses (OR=2.22, 95%CI:1.00–4.94; P-value=0.04) were some of the predictors of herb-drug interactions among cancer patients. Conclusion: The majority of cancer patients used herbal medicines during chemotherapy courses and physicians could reduce the odds of herb-drug interactions with proper education, monitor the side effects of chemotherapy, and prevent patients from self-medication with herbal medicines.