Background Cutaneous adverse drug reaction (CADR) is a common problem in clinical medication. This study aimed to investigate the correlation between clinical drug application and CADR occurrence as evidence for preventive strategies and rational clinical drug use. Methods We analyzed the characteristics of CADRs of 858 patients admitted to Shandong Provincial Third Hospital from March 2007 to December 2018. The most significant drugs concerning the common skin symptoms and their significance to CADR were investigated by case-non-case and multiple logistic regression analyses. Results A total of 266 drugs were involved in 858 cases of CADR. Among the ten most relevant medications, primarily antibiotics and herbal injections, and nutritional support drugs, potassium sodium dehydroandrographolide succinate injection, and cefoperazone sodium and sulbactam sodium injection were found to be 2.1 and 1.45 times statistically more prone to CADRs than to other adverse drug reactions (ADRs), respectively. The main route of administration was intravenous (63.16%), with oral administration accounting for 25.19%. There were 747 cases of ADR, 71 of severe ADR, 2 of new and severe ADRs, and 38 cases of new ADR. Overall, 100 cases of CADR exhibited abnormal alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels. The predictive factors for severe CADR occurrence included allergy and smoking histories, cefoperazone sodium, sulbactam sodium injection, levofloxacin lactate and sodium chloride injection. Conclusions Drug-induced CADR symptoms are commonly associated with other ARDs, predominantly rashes and pruritus, and are often accompanied by some medical conditions, especially liver and kidney damage. Detailed attention to a patient’s primary diseases, allergy history, and drug safety profile could help prevent or reverse CADR in most patients.