The invention discloses a preparation process of a positioning channeling blocking agent, and relates to the technical field of oil field development. The preparation process comprises the following steps: mixing ethanol, ethyl acetate, sodium lauryl sulfate, alkyl phenol polyoxyethylene (10) ether, ammonium persulfate, oxalic acid, furfuryl mercaptan, tripolycyanamide, formaldehyde, acrylonitrile and 2,6-toluene diisocyanate for reaction to obtain ammonium persulfate microcapsules; sequentially adding phenol and caustic soda into formaldehyde for reaction to generate phenolic resin; adding the ammonium persulfate microcapsules and the phenolic resin into a mixed solution of liquid acrylamide and tap water, and carrying out reaction at an ambient temperature of 80 DEG C to generate the positioning channeling blocking agent. The preparation process is simple, convenient, safe, and low in risk; by the preparation process, pollution of a plugging agent to a low-permeability layer can be reduced, movement of a gelatinized plugging agent in a stratum is avoided, and the plugging strength is ensured.