Sporozoites secrete proteins which can help them adhere to/invade host cells during gliding motility on the surface of host cells. Currently, the composition of secreted proteins of C. parvum during adhesion/invasion of host cells is not fully understood. In this study, TMT labeled quantitative proteomics was used for the first time to compare and analyze the secreted proteins of C. parvum in the gliding motility state (3 hpi) and adhesion/invasion state (6 hpi). Bioinformatics analysis of the quantified differentially secreted proteins from C. parvum and HCT-8 cells showed that a total of 626 and 2339 C. parvum and HCT-8 cells secreted proteins were quantified. Differentially secreted proteins of C. parvum are mainly modified after translation, which are related to protein degradation and kinase activity, and cap-domain proteins are highly expressed during sporozoite gliding motility. However, differentially secreted proteins of HCT-8 cells are mainly concentrated in the pathways related to extracellular matrix and cell adhesion molecules. This study identified some important molecules that may be involved in the interaction between C. parvum and HCT-8 cells, providing basic data for the screening of key functional genes and the study of invasion mechanism of C. parvum.