Cry1Fa-expressing corn and cotton have been commercially planted in U.S in order to effectively control several Lepidoptera pests. Making clear the cross-resistance of cotton bollworms (Helicoverpa armigera) to Cry1Ac and Cry1Fa and the synergism between the two toxins could provide the theoretical bases for rationally applying Cry1Fa+Cry1Ac cotton. The toxicity of Cry1Fa to the susceptible strain (96S) and the resistant strain (BtR, selected by Cry1Ac, the resistance ratio was 2 194.15-fold) was tested in our study. The results showed that the toxicity of Cry1Fa was lower than Cry1Ac to 96S, the LC50 value of Cry1Fa was 504.80 times as high as that of Cry1Ac, and there was 19.98-fold cross-resistance to Cry1Fa in the Cry1Ac-resistant strain (BtR). Cry1Fa mixed with Cry1Ac could increase the toxicity of Cry1Fa against 96S, and especially when the concentration of Cry1Fa was low, the synergistic effect was significant. However, the toxicity of Cry1Ac could be improved just when being added with high-dose Cry1Fa. Because the BtR strain had resistance to Cry1Ac, the toxicity of Cry1Ac to BtR reduced obviously. Mixing Cry1Fa into high-dose Cry1Ac could increase the mortality of BtR (P=0.0015, F=6.88, df=6), but the highest mortality was only 58.33%. The results of the 2-D-optimum orthogonal design experiment showed that Cry1Ac had significant effect to control the susceptible cotton bollworm (t1=13.76&amp;#65125;t0.05), and the influence of interactive effect between Cry1Ac and Cry1Fa on toxicity was also significant (t22=2.42&amp;#65125;t0.05&amp;#65307; t11=6.95&amp;#65125;t0.05&amp;#65307; t12=3.43&amp;#65125;t0.05). Cry1Ac and Cry1Fa had significant effect against the resistant cotton bollworm (t1=3.03&amp;#65125;t0.05&amp;#65307;t2=2.59&amp;#65125;t0.05), but Cry1Ac was the key determinant for the mortality of the susceptible and resistant cotton bollworms. The optimum concentration ranges of Cry1Ac and Cry1Fa were 1.41-2.10 &amp;#956;g/cm2. However, the interactive effect between Cry1Ac and Cry1Fa was not significant in the BtR resistant strain. Thus, although the crops expressing Cry1F+Cry1A can expand the spectrum of killing insects, however, because of the cross-resistance and the undesirable effect in managing the Cry1Ac-resistant bollworm, transgenic Cry1F+Cry1A cotton is not recommended for planting in China.