Abstract: In order to obtain suitable drying methods and provide high-quality raw materials for the storage and deep processing of Lentinula edodes (shiitake mushroom), the differences in multiple biomolecules (eritadenine, purine, total sugar, protein, amino acid and flavor compounds) among fresh and four methods (vacuum freezing, heat pump, hot air, and natural) dried shiitake mushrooms were systematically analyzed and compared. The results showed that the four drying methods could reduce the levels of eritadenine, purine, total sugar, protein and total amino acid content to varying degrees, while their impact on the ratio coefficient of essential amino acids and flavor compounds was not directional. Among the dried mushrooms, the contents of eritadenine, total sugar, protein, and amino acids in vacuum freeze-dried ones were similar to those in undried mushroom, while the total purine content was significantly reduced (P<0.05). Heat pump and hot air drying could significantly reduce the eritadenine, total sugar, and protein content of shiitake mushrooms (P<0.05), and had no significant advantages in amino acid and flavor substance retention, and total purine control. Natural drying could significantly reduce total sugar, protein, adenine and hypoxanthine content (P<0.05), while significantly increase the essential amino acid ratio coefficient (P<0.05). Based on the above results, it was recommended to use vacuum freeze-drying as the preferred method for preparing shiitake mushroom raw materials for processing high value-added products such as lipid and uric acid lowering products. Natural drying clould be used as a second choice. But it was not recommended to use heat pumps and hot air drying for the drying of shiitake mushroom raw materials, which would be used for the development of high-quality and high value-added products.