Objective: Hypersensitivity reactions with oxaliplatin (OXA) have attracted much attention. This study aimed to analyze the risk factors for OXA-induced hypersensitivity reaction in Chinese colorectal cancer patients through a single center retrospective investigation. Methods: The information from 459 colorectal cancer patients treated with OXA in a hospital was collected retrospectively to explore the risk factors for OXA-induced hypersensitivity reaction. Results: Among the 459 patients, 47 (10.24% incidence) cases developed hypersensitivity reactions, with a 3.70% incidence of grade III/IV reaction. The main symptoms included itching, flushing, dyspnea, and rash, which mainly involved skin and adnexa, respiratory system, and nervous system. Dexamethasone pretreatment presented no significant effects on the hypersensitivity reaction (P = 0.282). Multivariate analysis indicated that the previous allergic history (odds ratio (OR) 2.553, 95% confidence interval (CI) 1.139-5.721, P = 0.023) and OXA-free interval (OR 3.605, 95% CI 1.909-6.809, P = 0.000) were independent risk factors for OXA-induced hypersensitivity reaction. Conclusions: The incidence of OXA-induced hypersensitivity reaction in colorectal cancer patients was similar to those reported in other countries. Clinical medical staff should pay close attention to high risk factors, such as allergic history and patients having OXA-free intervals in order to avoid or alleviate hypersensitivity reactions.