ABSTRACT Shepherd's purse (Capsella bursa-pastoris [L.] Medik.) is a troublesome dicot weed that occurs in major wheat (Triticum aestivum L.) production areas in China. Tribenuron-methyl failed to control shepherd's purse in some fields in Runan County, Henan Province. This study aimed to establish the cross-resistance pattern of a resistant (R) population and explore the potential target-site and non-target-site based resistance mechanisms. Acetohydroxyacid synthase (AHAS) gene sequencing revealed a single nucleotide change of CCT to CGT resulting in the Pro to Arg substitution at amino acid position 197 in resistant individuals. Compared with the susceptible (S) population, R population displayed high level resistance to tribenuron-methyl. Cross resistance patterns showed that the R population was high resistant to flucarbazone-Na; moderately resistant to florasulam; low resistant to pyrithiobac sodium and pyroxsulam, and sensitive to imazethapyr. The pretreatment of malathion reduced the 50% growth reduction (GR50) value of tribenuron-methyl by 29% in the R population, suggesting that target-site resistance and non-target-site resistance mechanisms were both present in tribenuron-methyl -resistance of shepherd's purse. This is the first report of the acetolactate synthase Pro197Arg mutation in shepherd's purse.