Objective: Tizanidine is a medication commonly used to relieve muscle spasms and has a wide range of clinical applications. However, as its use has increased, reports of related adverse reactions have also risen. In-depth analysis of tizanidine’s adverse reaction patterns and potential safety risks through data mining is of great significance for guiding clinical decision-making and patient management. Methods: This study is based on the FAERS database, retrieving data from 2004 Q1 to 2025 Q1. The primary suspect drug was grouped, and the proportional imbalance method (ROR method) was used for signal detection of adverse drug events. Results: The adverse reactions of tizanidine are diverse and involve multiple systems, with nervous system diseases being the most common type of adverse event, accounting for 16.18% of the total reports. The proportion of adverse events reported by female and elderly patients is relatively high, and in terms of the outcome of adverse events, the proportion of hospitalizations is high, accounting for 30.31%, indicating a significant likelihood that tizanidine’s adverse events require hospitalization. Additionally, hypotension, drowsiness, drug ineffectiveness, and completed suicide are common adverse events, suggesting that the medication can cause significant central nervous system, cardiovascular, and mental health-related issues during its use. Signal mining using the ROR method shows high ROR values for adverse events such as potassium-losing nephropathy and decerebrate rigidity, indicating a potential causal relationship with tizanidine usage. Furthermore, the median time to the occurrence of adverse events after administration is 3 days, revealing that tizanidine-related adverse events often manifest shortly after administration, particularly within the first few days. Conclusion: The potential adverse reactions of tizanidine in clinical use, particularly those related to the nervous system, mental health, and cardiovascular aspects, warrant significant attention. Enhanced drug safety monitoring, especially individualized treatment and close monitoring in high-risk patient groups, can maximize the safety of medication use.