A high-throughput sequencing method for detecting methylated CpG islands comprises: (a) Treating a DNA sample with a modifying agent to form the modified DNA wherein cytosine bases but not 5'-methyl-cytosine bases of the DNA sample are modified to uracil bases; (b) Providing Primer A and DNA polymerase to the modified DNA to allow at least one round of linear amplification to form the semi-amplicon capable of anchoring Adapter Primer C at one end, wherein Primer A is composed of a 3' portion and a 5' portion, wherein the 3' portion contains 4 or more nucleotides capable of binding to the modified DNA and allowing amplification, wherein the 5' portion allows Adapter Primer C to bind to its reverse complementary sequence for PCR amplification; (c) Amplifying the semi-amplicon by using Primer B and DNA polymerase to form the full-amplicon of the original DNA enriched with methylated CpG islands and capable of anchoring Adapter Primer C at one end and Adapter Primer D at the other end, wherein Primer B is composed of a 3' portion and a 5' portion, wherein the 3' portion contains 7 or more nucleotides and is a high-CpG-density sequence capable of binding to the semi-amplicon and allowing amplification and enrichment of the methylated CpG islands, wherein the high-CpG-density sequence is a sequence of which the 3'-terminal 7 nucleotides contain 2 or 3 CpG dinucleotides, wherein the 5' portion allows Adapter Primer D to bind to its reverse complementary sequence for PCR amplification; (d) Amplifying the full-amplicon by using Adapter Primer C, Adapter Primer D and DNA polymerase to form the final-amplicon via PCR exponential amplification. (e) Separating and purifying the final-amplicon to form the library for high-throughput sequencing, sequencing the library and analyzing the data. (a) Treating a DNA sample with a modifying agent to form the modified DNA wherein cytosine bases but not 5'-methyl-cytosine bases of the DNA sample are modified to uracil bases; (b) Providing Primer A and DNA polymerase to the modified DNA to allow at least one round of linear amplification to form the semi-amplicon capable of anchoring Adapter Primer C at one end, wherein Primer A is composed of a 3' portion and a 5' portion, wherein the 3' portion contains 4 or more nucleotides capable of binding to the modified DNA and allowing amplification, wherein the 5' portion allows Adapter Primer C to bind to its reverse complementary sequence for PCR amplification; (c) Amplifying the semi-amplicon by using Primer B and DNA polymerase to form the full-amplicon of the original DNA enriched with methylated CpG islands and capable of anchoring Adapter Primer C at one end and Adapter Primer D at the other end, wherein Primer B is composed of a 3' portion and a 5' portion, wherein the 3' portion contains 7 or more nucleotides and is a high-CpG-density sequence capable of binding to the semi-amplicon and allowing amplification and enrichment of the methylated CpG islands, wherein the high-CpG-density sequence is a sequence of which the 3'-terminal 7 nucleotides contain 2 or 3 CpG dinucleotides, wherein the 5' portion allows Adapter Primer D to bind to its reverse complementary sequence for PCR amplification; (d) Amplifying the full-amplicon by using Adapter Primer C, Adapter Primer D and DNA polymerase to form the final-amplicon via PCR exponential amplification. (e) Separating and purifying the final-amplicon to form the library for high-throughput sequencing, sequencing the library and analyzing the data.