The thermal stability of sheepskin collagen cross-linked with chrome sulfate and mimosa (MI)–oxazolidine (OZ), respectively, had been researched in this experiment. All samples’ shrinkage temperatures (Ts) are determined by a special Ts-testing-apparatus and denaturation temperatures (Td) are determined by the differential scanning calorimetry. The relations between the modified collagens containing moisture and their hydrothermal stability, Ts or Td, were studied. The results show that the cross linking agents can enhance the thermal stability of modified collagen whose Ts are 109.8 and 110.6 °C for collagen treated with chrome and MI–OZ, respectively. When the samples contain 25–71.9% moisture for chrome leather and 20–71.1% for leather treated with MI–OZ, the hydrothermal stability will decrease with the increase of moisture. It was found that the difference between Ts and Td of collagen modified by chrome is more obvious than that of collagen modified with MI–OZ. And when the moisture of chrome leather exceeds 55%, Td cannot express thermal stability of modified collagen as a substitute for Ts, and the moisture is 40% for leather tanned with MI–OZ.