Objective To explore the mediating effect of coping modes between social support level and disease uncertainty in elderly inpatients with cerebral stroke. Methods Questionnaire investigation was performed on 208 elderly inpatients with cerebral stroke by using the Mishel Uncertainty in Illness Scale⁃Adult (MUIS⁃A), Social Support Rating Scale (SSRS), and the Medical Coping Modes Questionnaire (MCMQ). The correlations between the scores of various scales were analyzed, and the linear regression model was used to analyze the mediating effect of coping modes between social support level and disease uncertainty in elderly inpatients with cerebral stroke. Results Patients obtained the total score of MUIS⁃A of 90.79±14.60, total score of SSRS of 37.89±6.95, and scores of confrontation, avoidance, and yielding dimensions of MCMQ of 15.91±4.14, 15.88±2.75, and 9.44±3.83, respectively. The total score of MUIS⁃A negatively correlated with score of confrontation dimension of MCMQ and SSRS total score, and positively correlated with MCMQ yielding dimension score (P<0.05); furthermore, SSRS total score positively correlated with scores of confrontation dimension and avoidance dimension of MCMQ, and negatively correlated with score of yielding dimension of MCMQ (P<0.05). The results of mediating effect revealed that there was no mediating effect of confrontation coping mode between social support level and disease uncertainty, while there was a perfect mediating effect of yielding coping mode between the two. Conclusion Social support level negatively correlates with disease uncertainty in elderly inpatients with cerebral stroke, and there is a perfect mediating effect of yielding coping mode between the two as above. Medical and nursing staff should not only pay attention to evaluate coping modes on diseases in patients and take targeted interventions to change patients' negative coping modes on diseases, but also pay attention to patients' social support status and provide adequate social support for patients, so as to reduce disease uncertainty.