Hydrodeoxygenation (HDO) of lignin derivatives at room‐temperature (RT) is still of challenge due to the lack of satisfactory activity reported in previous literature. Here, it is successfully designed a Pd/UiO‐66‐(COOH)2 catalyst by using UiO‐66‐(COOH)2 as the support with uncoordinated carboxyl groups. This catalyst, featuring a moderate Pd loading, exhibited exceptional activity in RT HDO of vanillin (VAN, a typical model lignin derivative) to 2‐methoxyl‐4‐methylpheonol (MMP), and >99% VAN conversion with >99% MMP yield is achieved, which is the first metal‐organic framework (MOF)‐based catalyst realizing the goal of RT HDO of lignin derivatives, surpassing previous reports in the literature. Detailed investigations reveal a linear relationship between the amount of uncoordinated carboxyl group and MMP yield. These uncoordinated carboxyl groups accelerate the conversion of intermediate such as vanillyl alcohol (VAL), ultimately leading to a higher yield of MMP over Pd/UiO‐66‐(COOH)2 catalyst. Furthermore, Pd/UiO‐66‐(COOH)2 catalyst also exhibits exceptional reusability and excellent substrate generality, highlighting its promising potential for further biomass utilization.