Background: Acceptance of pain is one of the most significant topics in the field of chronic pain due to its influence on the adaptation and response of people. Also, chronic pain and pain caused by the progress of cancer have a high prevalence in all stages and types of cancer. Aims: The present study aimed to predict the acceptance of chronic pain in patients with cancer based on anxiety sensitivity and emotional suppression with the mediating role of learned helplessness. Methods: The current research method was descriptive-correlation and structural equation modeling. A number of patients with cancer (400), admitted to the oncology department of Imam Khomeini Hospital in Ardabil City of Iran in the second half of 2022, were selected as the convenience sample and responded to McCracker et al.’s chronic pain acceptance scale, Rees et al.’s anxiety sensitivity scale, Roger and Nasho’s emotional control questionnaire, and Quinles and Nielson’s learned helplessness questionnaire. Results: Based on the obtained results, the causal relationship between anxiety sensitivity, emotional suppression, learned helplessness, and acceptance of chronic pain in patients with cancer was confirmed based on various fit indices. Anxiety sensitivity, emotional suppression, and learned helplessness had a direct effect on the acceptance of chronic pain in patients with cancer. Moreover, anxiety sensitivity and emotional suppression through learned helplessness had indirect effects on pain acceptance in patients with cancer (p < .05). Conclusions: Thus, anxiety sensitivity, emotional suppression, and learned helplessness play an essential role in the level of pain acceptance in patients with cancer, and targeting these three components through psychological treatments can be effective in the level of pain acceptance in these patients.