The invention discloses a preparation method of lenalidomide or its acid salt. The preparation method comprises the following steps that a, 3-aminopiperidine-2,6-dione or its acid salt and a compound shown in the formula I undergo a condensation reaction under alkaline conditions to produce a compound 3-(4-nitro-1-oxo-1H-isoindole-2-yl)piperidine-2,6-dione shown in the formula II, and b, the compound shown in the formula II undergoes a catalytic hydrogenation reaction to produce lenalidomide or its acid salt. The preparation method has a reaction route shown in the description, wherein R1 represents phenyl, benzyl, C1-6 alkyl or C3-6 cycloalkyl and R2 represents benzenesulfonyl, p-toluenesulfonyl, methylsulfonyl, acetyl or trifluoroacetyl. The preparation method does not utilize the existing hypertoxic reagent, has the advantages of easy acquisition and low prices of raw materials, low toxicity, simple operation, safety and environmental friendliness and satisfies industrial production requirements.