Panax notoginseng (PN) has been used as a qi- and blood-activating (Huoxue) drug for thousands of years in China. It has also been widely used as an anticancer drug at present. As a Huoxue drug, the effect of PN on hematopoietic differentiation in tumor-bearing body has been paid more and more attention. Our research found that panax notoginseng saponins (PNS), especially panaxadiol saponins (PDS) and its aglucon 20(S)-Protopanaxdiol (PPD), could improve the immunosuppressive state by regulating the abnormal hematopoietic differentiation in a tumor-bearing body by multiple ways. An interesting phenomenon is that PDS reduced the neutrophil-lymphocyte ratio (NLR) via its inhibition effect on the granule-monocyte differentiation of spleen cells, which is associated with a decrease in the secretion of tumor MPO, G-CSF, PU.1, and C/EBPα. Otherwise, PDS increased the proportion of both hematopoietic stem cells and erythroid progenitor cells in the bone marrow, but inhibited spleen erythroid differentiation via inhibiting secretion of tumor EPO, GATA-1, and GATA-2. This study suggests that PNS regulated the tumor-induced abnormal granule-monocyte differentiation of hematopoietic stem cells, affecting the distribution and function of haemocytes in tumor-bearing mice.