Conformational changes and specific interactions in the collagen/hyaluronic acid blends were studied by two-dimensional infrared correlation spectroscopy with the interruption of the component of hyaluronic acid in collagen/hyaluronic acid blends.It was found that the synchronous cross-peaks, derived from stretching vibrations of CO at 1 694 cm-1, wagging of N—H at 1 524 cm-1 and in-plane deformation of N—H at 1 241 cm-1 of collagen, were indicative of local conformational changes of collagen.The synchronous negative cross-peak between stretching vibrations of C—OH of hyaluronic acid at 1 045 cm-1 and streching vibrations of CO of collagen at 1 694 cm-1 suggested that the interaction of hydrogen bonding existing between O—H of HA and CO of collagen with the content of HA varied from 0% to 50%.With the content of HA more than 50%, the cross-peak at 1 045 cm-1 disappeared in synchronous correlation spectra while the intensity of cross-peak at (1 694, 1 524), (1 694, 1 241), (1 524, 1 241) increased, which indicated that no interaction was found between O—H of HA and collagen, however, the interactions of hydrogen bonding existed between CO of HA and N—H of collagen, resulting in the conformational changes of collagen.