Abstract: To explore the potential of the synergism of Pythium oligandrum (PO) combined with Oxathiapiprolin (OX) against tobacco black shank, the biocompatibility of PO and OX, as well as the toxicity of OX, PO and OX+PO against Phytophthora nicotianae were measured by the growth rate method and flat confrontation method, while the synergistic antifungal effect and the growth promotion of tobacco were determined in vivo. The biocompatibility test showed that the growth rate of PO with different concentrations of OX treatments has no significant difference from that of the blank control. The results of in vitro toxicity test indicated that the inhibition rate of OX at 8.0×10^-3 mg/L on P. nicotianae was 91%, EC₅₀=2.19×10^-3 mg/L, while that of OX (1.0×10^-3 mg /L) + PO was 96.31%. The results of pot experiment showed that the control effect of the OX+PO treatment was the highest (84.57%), which was 8.76% and 10.49% higher than that of OX (77.76%) or PO (76.54%) treatment alone, respectively. The combined use of OX and PO had a significant promotion on tobacco growth, and the plant height, stem diameter, leaf length and leaf width were increased by 57.10%, 20.21%, 33.62% and 35.08%, respectively, compared with the control treatment. The above results indicated that the combined use of PO and OX can effectively reduce the amount of OX used, improve the disease prevention effect, and promote the growth of tobacco.