Abstract Background Tumour associated antigen L6 (TAL6) is a cell surface protein of the transmembrane-4 superfamily (TM4SF) also known as TM4SF1. TAL6 is over-expressed in more than 80 % of human lung, breast, colon and ovarian tumours but not normal tissues. Synthetic peptides are attractive for cancer immunotherapy because of their safety and flexibility. We have identified an B cell epitope of TAL6 using monoclonal antibodies. The synthetic peptide epitope formulated with adjuvants can induce anti-tumour immunity. Methods The linear B cell epitope was identified by anti-TAL6 monoclonal antibody using overlapping peptides cover the extracellular domain of TAL6. The synthetic peptide containing B cell epitope was formulated with different adjuvants to immunize mice to determine their immunogenecity. Furthermore, the sera of immunized mice were used to examine the antibody-dependent cellular cytotoxicity (ADCC) against human cancer. Moreover, the anti-tumor effects were evaluated in mouse model. Results The anti-TAL6 recognized a minimal linear region at amino acid 121-129. We formulated synthetic peptide (a.a.114-133) and a pan-DR peptide with different adjuvants to immunize mouse and evaluate their immunogenicity. The peptides formulated with an emulsion type nanoparticle (PELC) adjuvant and a toll-like receptor 9 agonist (CpG ODN) (PELC/CpG) induced the greatest ADCC responses in TAL6-expresssed cell lines. The induced anti-tumor immunity inhibited the growth of TAL6-positive cancer cells in mouse. Conclusions These data suggested that a peptide containing B cell epitopes of TAL6 formulated with PELC/CpG adjuvant is feasible for cancer immunotherapy. Legal entity responsible for the study The authors. Funding Ministry of Science Technology, Taiwan. Disclosure All authors have declared no conflicts of interest.