The invention relates to the technical field of biological detection, in particular to a leukemia B cell minimal residual detection method. According to the invention, 10 upstream primer sequences are designed directed at a variable V region of human PCR, 1 downstream primer sequence is designed respectively directed at A, D, M, G gene constant regions of BCR, 2 downstream primer sequences are designed directed at an E gene constant region of BCR, and multiplex PCR is carried out to amplify a target sequence, after purification of the target sequence, a basic group A is added to the 3' end of the product sequence and the product is connected to an adapter sequence, the connection product containing the adapter is subjected to PCR amplification with sequencing primers so as to obtain an amplification product, and then purification and sequencing are carried out, and the sequencing result is compared with a cancer cell RNA amplification product sequence. The method has sensitivity up to 10<-6>, and wide detection coverage, and can detect almost all B cell receptors.