Introduction We aimed to measure the acceptability towards the COVID-19 vaccination in cancer patients and to investigate determinant factors associated with the patient's choice. Methods We conducted a cross-sectional survey with a self-administered questionnaire delivered to 329 cancer patients in 3 oncology cancer centers in Tunisia between February-May 2021. Logistic regression was used to evaluate odds ratio predicting patient's intentions toward the vaccine. Results Acceptance rate was 50.5%, 28.3% (n = 93) reported to definitely refuse the vaccine and 21.2% (n = 70) did not make their decision yet. High educational level, history of comorbidities, history of influenza vaccination in the current season, and patient's opinion about the severity of COVID-19 did not predict vaccine resistance. However, patients who think that the vaccine may interfere with treatment efficacy (OR = 7.28, 95%CI [2.5-12.32]), or may impact cancer outcome (OR = 6.14, 95%CI [2.27-16.7]), were significantly more likely to refuse the vaccine. Patients who disagree that the vaccine is a major weapon against the pandemic (OR = 6.07, 95%CI [2.34-9.52]) or that it could reduce the virus transmission (OR = 7.34,) were also significantly more likely to reject the vaccination. Safety concerns were also significant predictive factors (OR = 7.9, . Confidence level in the authorities played a significant role in patient's acceptance of the vaccine, indeed patients who are not registered (OR = 5.9, or not informed about the Tunisian national vaccination platform EVAX (OR = 5.51, 95%CI [2.1-7.9]) were more likely to be against the vaccine. Conclusion Cancer patient's education about the impact of the vaccine on their disease and on the COVID-19 is needed. Governments should build strategies to gain more population confidence.

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