Hydrogels are important in biological and medical applications, such as drug delivery and tissue engineering. DNA hydrogels have attracted significant attention due to programmability and biocompatibility of the material. We developed a series of low-cost "one-strand" DNA hydrogels self-assembled from single-stranded DNA monomers containing multiple palindromic domains. This new hydrogel design is simple and programmable. Thermal stability, mechanical properties, and loading capacity of the one-strand DNA hydrogels can be readily regulated by simply adjusting the DNA domains.