The invention discloses a detection method for low-frequency mutation of circulating tumor DNA (which is called as ctDNA for short in following). The method comprises the following steps: S1, extracting cfDNA from blood plasma; S2, repairing the tail end of the extracted cfDNA and adding A at the 3' end; S3, performing connector connection on a tail end repaired product, wherein a connector contains a random molecular tag sequence and contains an index sequence for distinguishing different samples; S4, performing PCR amplification on a connector connection product; S5, obtaining a target library through a probe; S6, sequencing through illumina Miseq, illumina Nextseq, illumina Hiseq platforms and analyzing offline data. The method is suitable for probe target capturing sequencing, can reduce an offline data repetition rate, can remove PCR and errors generated in a sequencing process, can improve ctDNA detection flexibility and specificity and can reduce a false positive rate.