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 H2O molecules on thermal expansion. The in situ synchrotron X-ray diffraction results showed that the as-prepared TiCo(CN)(6)center dot 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 (alpha(1) = -4.05 x 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 H2O 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 H2O 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.