Abstract: The weed control efficacy and the safety to cotton of the combination of flumioxazin and pendimethalin were evaluated. Whole-plant dose response experiments were conducted in greenhouse to evaluate the joint effect type, the safety to different cotton varieties, and the selectivity index of the mixtures. Weed control efficacy and response of cotton to the mixtures were also investigated in field experiments. The results of greenhouse study showed that the joint effect type was either additive or synergistic when flumioxazin was mixed with pendimethalin for the control of Portulaca oleracea, Amaranthus retroflexus and Digitaria sanguinalis. When the mass ratio was 1 : 10, the weed control efficacy of the mixtures was higher than that of pendimethalin applied alone. The selectivity index between cotton varieties and weeds tested was in the range of 25.81–39.39, which suggested the safety of the mixtures to cotton was improved compared with that of flumioxazin and pendimethalin used alone. The results of field experimensts showed that the mixtures of flumioxazin and pendimethalin had good efficacy against Acalypha australis, A. retroflexus, P. oleracea, Chenopodium album and Eleusine indica and was safe to cotton.