Globally, weeds interfere with agricultural production activities and have a very serious impact on agriculture and animal husbandry. Identifying a safe and reliable weed control strategy might increase yield, production net income, and improve crop quality. A field experiment was carried out to explore the effects of weeds interference frequency on the yield and quality of Glycyrrhiza uralensis Fisch in an arid and semi-arid area of northwest China. The experiment consisted of seven treatments and were (1) no weeding, marked as WF0; (2)-(7) artificial weeding by hoe once every 1, 2, 4, 6, 8, 10 weeks after emergence, marked as WF1, WF2, WF4, WF6, WF8 and WF10, respectively. We found that the higher weeding frequency had a higher the plant height, photosynthesis, yield and quality. The highest yield was obtained in the WF1 treatment, while the cost of weeding was the highest among all treatments. The concentration of liquiritin and glycyrrhizic acid were increased by 53.24% and 36.57%, with the highest nitrogen metabolism enzymatic activities and quality in WF4 treatment. WF4 treatment exhibited the largest increases in the net income among all treatments in both growing seasons, with respective increases up to 71.39 % and 78.81%. These findings suggested that weeding once every 4 weeks would be an effective and sustainable measure to control weeds in an arid and semi-arid area.