Method for detecting and/or for the prognosis of a Head and Neck Squamous Cell Carcinoma (HNSCC) comprising the steps of: (i) Purifying the genomic DNA from an isolated sample obtained from an individual; (ii) Treating the genomic DNA, with bisulfite, preferably sodium bisulfite; (iii) Amplifying the genomic DNA, after step (ii) by using at least one primer pair said primer pair allowing the amplification of at least one sequence of the genomic DNA region of each one of the genes comprised in the following set of genes: (b) LRRTM1, PARP15, ZAP70, miR193, miR296, hTERT and, optionally, of at least one of the following genes: FLI1, LINC00599, GP1BB, EPHX3, ITGA4, NTM, KIF1A, wherein said sequence comprises at least one CpG and/or CpG island; (iv) Measuring the methylation level of the CpG and/or CpG island falling in the sequence amplified according to the step (ii) and belonging to the following set of genes: LRRTM1, PARP15, ZAP70, miR193, miR296, hTERT and, optionally, of at least one of the following genes: FLI1, LINC00599, GP1BB, EPHX3, ITGA4, NTM, KIF1A; wherein the hypermethylation of the at least one CpG and/or CpG island falling in the sequence of at least one of the following genes of the sets: EPHX3, KIF1A, LRRTM1,FLI1, ITGA4, LINC00599, NTM, PARP15, ZAP70, miR193 and/or the hypomethylation of the at least one CpG and/or CpG island falling in the sequence of at least one of the following genes of the sets: miR296, GP1BB, hTERT is(are) indicative of a HNSCC positive sample wherein the hypermetylation and/or the hypomethylation is(are) evaluated compared to the methylation level measured in a sample isolated from an healthy individual. (i) Purifying the genomic DNA from an isolated sample obtained from an individual; (ii) Treating the genomic DNA, with bisulfite, preferably sodium bisulfite; (iii) Amplifying the genomic DNA, after step (ii) by using at least one primer pair said primer pair allowing the amplification of at least one sequence of the genomic DNA region of each one of the genes comprised in the following set of genes: (b) LRRTM1, PARP15, ZAP70, miR193, miR296, hTERT and, optionally, of at least one of the following genes: FLI1, LINC00599, GP1BB, EPHX3, ITGA4, NTM, KIF1A, wherein said sequence comprises at least one CpG and/or CpG island; (iv) Measuring the methylation level of the CpG and/or CpG island falling in the sequence amplified according to the step (ii) and belonging to the following set of genes: LRRTM1, PARP15, ZAP70, miR193, miR296, hTERT and, optionally, of at least one of the following genes: FLI1, LINC00599, GP1BB, EPHX3, ITGA4, NTM, KIF1A; wherein the hypermethylation of the at least one CpG and/or CpG island falling in the sequence of at least one of the following genes of the sets: EPHX3, KIF1A, LRRTM1,FLI1, ITGA4, LINC00599, NTM, PARP15, ZAP70, miR193 and/or the hypomethylation of the at least one CpG and/or CpG island falling in the sequence of at least one of the following genes of the sets: miR296, GP1BB, hTERT is(are) indicative of a HNSCC positive sample wherein the hypermetylation and/or the hypomethylation is(are) evaluated compared to the methylation level measured in a sample isolated from an healthy individual.