The application of non-noble metal supported catalysts in the hydroisomerization of long-chain n-alkanes is a novel field, and there is currently not any research available on the deactivation process of these catalysts. We investigated into the deactivation mechanism of NiWS/SAPO-11 catalyst in the hydroisomerization of n-hexadecane in this work for the first time. Specifically, coke deposition behavior and active phase migration were investigated. The reduction of catalytic efficiency of the catalyst was partially aided by the decrease in specific surface area, pore volume, and acid density. From the perspective of the active phase, the clusters of NiWS active phase migrated as the reaction time increased, mostly resulting in an increase in both the stacking number and the length of active phase slabs. The migration of active phase increased the distance between active phase clusters and metal sites, and decreased the utilization ratio of active metal atoms. From the perspective of coke deposition, the coke formed on the catalyst includes soft coke and hard coke. The formation and evolution of coke on the catalyst were investigated. The soft coke (aliphatic compounds) progressively transformed into hard coke (polycyclic aromatic hydrocarbons and graphite-like), and the coke gradually migrated from the external surface of the catalyst to the pore channels as the reaction time increased. It is expected to provide theoretical basis and reference value for the deactivation research and design of non-noble metal supported hydroisomerization catalyst.