OBJECTIVE To evaluate and analyze real-world post-marketing adverse drug reactions(ADRs) of sindilizumab and provide critical reference for safe clinical medication. METHODS The data were sourced from the National Adverse Drug Reaction Monitoring System database, covering ADR reports related to sindilizumab in Beijing area in the past five years. These reports identified sindilizumab as the suspected drug to the ADRs. Statistical analysis was conducted using SPSS 22.0 software. RESULTS A total of 155 sindilizumab-related ADR reports were analyzed. In terms of gender distribution, the ratio of male to female patients was 1.77∶1. Skin reactions were the most common ADRs reported. Allergic reactions dominated ADR reports occurring within 24 hours. Severe ADRs accounted for 26.45% of the reports, with most severe reactions occurring after 24 hours of medication use (P=0.005). In patients with tumors not included in the approved indications, the risk of experiencing severe ADRs was significantly higher compared with those with indicated conditions (P=0.006). Nine patients experienced ADRs due to drug dosages exceeding the recommended dosage in the instructions. Additionally, the concomitant use of the drug with lenvatinib was associated with the emergence of new safety signals, including myocardial infarction and diabetic ketoacidosis, necessitating heightened vigilance in clinical practice. CONCLUSION This investigation has uncovered an augmented risk of severe ADRs in individuals receiving medications for non-indicated uses. Consequently, implementation of stricter surveillance measures is needed for patients with off-label conditions to facilitate timely medical interventions. Notably, a significant incidence of severe ADRs is observed to occur beyond the initial 24-hour period following treatment. Thus, individuals receiving the drug in day-care unit should be explicitly instructed to closely monitor their post-medication health status upon discharge and to seek immediate medical consultation in case of any arising discomfort. There exists noncompliance with the recommended dosage, thus attention should be paid to such cases. Moreover, concurrent use of sindilizumab with lenvatinib has been identified to induce myocardial infarction and diabetic ketoacidosis, representing a new safety signal that demands clinical caution.