Abstract: In recent years, the rapid increase in yield and consumption of packaging cushioning foamed plastics, such as expandable polystyrene (EPS) , has led to increasingly serious environmental and health issues. In addition, the agricultural straw such as reed straw is being underutilized, resulting in wasted resources and environmental pollution. Recently, a novel biodegradable packaging material, mycelium composite material is attracting more interests to replace foamed plastics. Mycelium composite material is produced by using fungi strains to degrade agricultural straw, thus helping to improve the utilization rate of agricultural straw. In order to optimize the preparation process of mycelium composite materials with high compressive property, this study investigated the effects of fungi strains, inoculum amounts, substrate types, particle sizes on the compressive property of mycelium composite material by using compressive strength as the evaluation index. A total of ten fungi strains, including Ganoderma resinaceum, Pleurotus ostreatus, P. sajor-caju, Trametes sanguinea, P. geesteranus, Flammulina filiformis, Agrocybe aegerita, Pholiota squamosa, Lentinus edodes, Hericium erinaceus, were inoculated into kenaf and cottonseed hull compound substrate to cultivate mycelium composite material. Results showed that the compressive strength of G. resinaceum group was significantly higher than other strains, maybe due to compact external mycelial layer and tight hyphal network. The high growth rate was also attributed to more compact mycelium network structure. After inoculating G. resinaceum into 17 substrates, including noil, kenaf, reed straw, cottonseed hull, corn cob, sawdust and eleven compound substrates composed of the above six raw materials, the best compressive strength was achieved in the RCC group (reed straw and corn cob). The reason may be that reed straw and corn cob could provide appropriate void structure and sufficient nutrients, which is conducive to build dense hyphal network. Then G. resinaceum was inoculated into RCC for particle sizes and inoculum amounts optimization experiment. The compressive strength achieved highest value in substrate with a wide range of particle size (0.075～2.000 mm). The combination of substrate with large and small particle sizes could provide suitable nutrition and growth space, thus promoting the formation of a dense network structure of mycelia. The highest compressive strength was achieved in the 7.5% of inoculum amount. The mycelium colonization was weak under the case of low inoculum amount, resulting in lower compressive strength of the material. Meanwhile, excessive inoculation amount also caused the mycelia to compete for nutrients and space, thus reducing the density of the mycelium network structure and decreasing the compressive strength of the material. Collectively, the mycelium composite material produced under the following conditions showed high compressive strength and good buffering performance: G. resinaceum as the tested strain, reed straw and corn cob as the compound matrix, 0.075～2.000 mm of particle size, 7.5% of inoculum amount. The compressive strength of the obtained mycelium composite material could reach 190.99 kPa at 10% relative deformation, which was 1.9 times that of 18.0 kg/m³ EPS. Findings here could provide a reference to optimize the process parameters and compressive property of mycelium composite material, and has positive significance for improving comprehensive utilization of agricultural by-products such as reed straw.