Safflower is an annual herb of Compositae, which has great economic value. To explore the impact of invasive weed Xanthium italicum Moretti on the economic crop safflower, field experiments were conducted, the growth-related characters and the relative intensity of competition between the two species was explored. The results showed that under monoculture conditions, the stem height, crown width, stem diameter and the biomass of X. italicum root, stem and leaves were 1.14, 1.96, 1.82, 4.42, 4.21 and 3.99 times as high as those of safflower, respectively. When the two species coexisted, the growth related characters of X. italicum were further significantly improved, while the growth related characters of safflower were significantly decreased. When coexisted with X. italicum, the corolla biomass, hydroxysafflor yellow A content of corolla, seed yields, 100-seed weight, and seed oil content of safflower in the interplanted treatment 90.04%, 33.11%, 63.89%, 40.58%, and 25.61% lower than those in the monocultured treatment, respectively. Relative yield (RY) and Competitive balance index (CB) of X. italicum and safflower showed that the interspecific competitiveness of X. italicum was significantly higher than that of safflower. Under the competitive inhibition of X. italicum, not only the vegetative growth, but also the reproductive growth, yield, and quality of the economic organs of safflower were significantly negatively impacted. Together, our findings provide important scientific basis for evaluating the invasion risks and consequences of safflower’s cropland ecosystem by X. italicum.