The invention discloses a novel loofa sponge shoe sole and application and manufacturing method thereof. The novel loofa sponge shoe sole is provided with an EVA insole, and a loofa sponge tablet is attached to the upper surface of the EVA insole in an integral hot pressing. The novel loofa sponge shoe sole can be applied to various types of shoes. The manufacturing method of the novel loofa sponge shoe sole includes the following steps that firstly, loofa sponge is preprocessed, wherein a raw loofa sponge tablet is obtained through preprocessing; secondly, the tablet is cut according to the figure, wherein the loofa sponge tablet in the required size and shape is obtained by cutting the raw loofa sponge tablet; thirdly, hot pressing forming is conducted, wherein the lower surface of the loofa sponge tablet and the upper surface of the EVA insole are attached together through glue and formed in an integral hot pressing mode, and the loofa sponge shoe sole is manufactured. By means of reasonable and optimized design, the shoe sole has excellent, lasting and effective shock absorption, moisture absorption, good foot feeling and other comfortable properties, and is high in practicality, natural and environmentally friendly.