Abstract: The structural properties of single DNA molecules treated with the anticancer drug cisplatin were studied with magnetic tweezers and atomic force microscopy (AFM). Under the effect of low-concentration cisplatin (tens of μM), the DNA became more flexible, with the persistence length decreased significantly from ~52 to ~15 nm. At a high drug concentration (hundreds of μM), a DNA condensation phenomenon was observed. Based on the experimental results from both single-molecule and AFM studies, we propose a cisplatin-induced DNA softening-looping-shortening-condensing model to explain this kind of DNA condensation. We think the observed micro-loop structure formation of DNA due to distant crosslinks may be an important feature of the effect of platinum anticancer drugs.