Objective: In cancer care, optimal communication between patients and their physicians is, among other things, dependent on physicians' emotion regulation, which might be related to physicians' as well as patients' characteristics. In this study, we investigated physicians' emotion regulation during communication with advanced cancer patients, in relation to physicians' (stress, training, and alexithymia) and patients' (sadness, anxiety, and alexithymia) characteristics. Methods: In this study, 134 real-life consultations between 24 physicians and their patients were audio-recorded and transcribed. The consultations were coded with the “Defence Mechanisms Rating Scale—Clinician.” Physicians completed questionnaires about stress, experience, training, and alexithymia, while patients completed questionnaires about sadness, anxiety, and alexithymia. Data were analysed using linear mixed effect models. Results: Physicians used several defence mechanisms when communicating with their patients. Overall defensive functioning was negatively related to physicians' alexithymia. The number of defence mechanisms used was positively related to physicians' stress and alexithymia as well as to patients' sadness and anxiety. Neither physicians' experience and training nor patients' alexithymia were related to the way physicians regulated their emotions. Conclusions: This study showed that physicians' emotion regulation is related to both physician (stress and alexithymia) and patient characteristics (sadness and anxiety). The study also generated several hypotheses on how physicians' emotion regulation relates to contextual variables during health care communication in cancer care.