The invention provides a preparation method and a key intermediate of an anticoagulant apixaban. The method comprises the following steps: (1) by taking N-(4-nitrophenyl)-3,3-dichloro-2-oxopiperidine (compound 15) as an initial raw material, carrying out a reduction reaction to obtain a compound 16; (2) carrying out an acylation reaction between the compound 16 and 5-valeryl chloride bromine to obtain a compound 17; (3) reacting the compound 17 to obtain a compound 18 in the presence of a cyclic condensation agent; (4) carrying out an elimination reaction between the compound 18 and alkali to obtain a compound 19; (5) reacting the compound 19 with a compound 4 to obtain a compound 6; and (6) finally performing ammonolysis on the compound 6 to obtain apixaban. The method has the advantages that (1) the synthetic route is more reasonable; (2) an expensive or toxic reagent with high irritation is avoided; (3) reaction by-products are fewer and are easily purified; (4) the total yield is high; and (5) the reaction is suitable for industrial production. The reaction route is shown as the following formula.