Understanding the role of guest molecules in the lattice void of open-framework structures is vital for tailoring thermal expansion. Here, we take a new negative thermal expansion (NTE) compound, TiCo(CN) 6 , as a case study from the local structure perspective to investigate the effect of H 2 O molecules on thermal expansion. The in situ synchrotron X-ray diffraction results showed that the as-prepared TiCo(CN) 6 •2H 2 O has near-zero thermal expansion behavior (100−300 K), while TiCo(CN) 6 without water in the lattice void exhibits a linear NTE (α l = −4.05 × 10 −6 K −1 , 100−475 K). Combined with the results of extended X-ray absorption fine structure, it was found that the intercalation of H 2 O molecules has the clear effect of inhibiting transverse thermal vibrations of Ti−N bonds, while the effect on the Co−C bonds is negligible. The present work displays the inhibition mechanism of H 2 O molecules on thermal expansion of TiCo(CN) 6 , which also provides insight into the thermal expansion control of other NTE compounds with open-framework structures.