Fuzheng Qingjie (FZQJ) is a polyherbal Chinese medicine that has previously been implemented as an adjuvant therapy for gastrointestinal cancer. The present study investigated whether FZQJ is able to potentiate the anticancer effect of cyclophosphamide (CTX). Hepatoma 22 tumor-bearing mice were randomly divided into a vehicle group, CTX group, FZQJ group and combination (CTX+FZQJ) group. In addition, untreated mice without H22 cells served as blank controls. Seven days post-treatment, the mice were sacrificed and the tumors were weighed. Blood cells were evaluated using an automatic hemocytometer analyzer and flow cytometer. The expression levels of interleukin (IL)-2 and tumor necrosis factor (TNF)-α were evaluated using a radioimmunoassay. Apoptotic cells were observed using a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Alanine transaminase, aspartate aminotransferase, blood urea nitrogen and creatinine were examined using an automatic biochemical analyzer. The results demonstrated that the tumor inhibitory rate and apoptosis index were higher in the combination group, compared with those in the CTX group. Notably, FZQJ was able to alleviate CTX-induced decreases in the numbers of white blood cells and platelets, CD3+ and CD4+ T lymphocyte subsets, and the concentration of hemoglobin, body weight and thymus index, and increase serum TNF-α and IL-2 levels without overt hepatorenal toxicity. These results suggest that FZQJ granules may enhance the anticancer effect of CTX, in addition to alleviating the side effects.