The aim of this study was to analyze the clinical efficacy of Apatinib plus Ba Zhen granules in advanced unresectable differentiated thyroid cancer and its influence on immune factors. Sixty patients with advanced unresectable differentiated thyroid cancer in our hospital between January 2018 and December 2019 were selected and randomized to the control group and the observation group (30 cases in each group). After treatment, the observation group yielded higher serum levels of Cyfra21.1 and Gal-3, but lower SIL-2R levels than the control group. After treatment, the two groups obtained a marked increase in CD3+ and CD4+ levels and a decrease in CD8+ level, in which the observation group has higher levels of CD3+ and CD4+ and lower levels of CD8+ than the control group. After treatment, the serum FT3 and FT4 levels sharply increased and serum TSH levels declined significantly, with higher levels of FT3 and FT4 and lower levels of TSH observed in the observation group. The incidence of adverse reactions didn't significantly differ between groups. In advanced unresectable differentiated thyroid cancer, apatinib remarkably inhibits disease development. The combination of Apatinib and Ba Zhen granules adjusts immune factors and improves thyroid function, with a low incidence of adverse reactions and promising efficacy.