Objective: To explore the regulation of fucoidan (FUC) as a functional food on immune function and intestinal flora in immunocompromised mice. Methods: Forty male BABL/C mice were randomly divided into 4 groups. The intervention group was given high and low doses of fucoidan for intragastric intervention every day for 28 consecutive days. The control group and model group were given equal volume of normal saline every day. Except for the normal group， the other groups were intraperitoneally injected with cyclophosphamide on the 24th day to construct an immunocompromised mouse model. Enzyme-linked immunosorbent assay， flow cytometry， HE staining， high-throughput sequencing of 16S rRNA gene of intestinal microbiota， etc. were used to detect the changes of mouse immune function and intestinal flora. Results: Compared with the normal group of mice， the immune function of the model group was significantly decreased， and the spleen and intestinal tissues were severely damaged. After FUC intervention， the morphological damage of the spleen and colon tissues was significantly improved (P<0.05). At the same time， FUC alleviated the increase of inflammatory factor levels in serum (P<0.05). Besides， the content of Bacteroides in the cecal content of the model group mice was significantly increased (P<0.05)， Lactobacillus and Roseburia were significant decrease (P<0.05) compared with the normal group. After FUC intervention， the imbalanced intestinal flora was restored in model mice， and the composition structure of intestinal flora was approached the normal group. Conclusion: FUC can effectively improve the immune function and alleviate the intestinal mucosal damage in immunocompromised mice. The mechanism may be related to the change of intestinal flora.