Recently, combinations of conventional chemotherapeutic agents with compounds were reported and have proven to be effective in synergistically restricting tumor growth and reducing side effects caused by toxicity.49,50 Based on above principles, therapeutics targeting the ELFN1-AS1/EZH2-DNMT3a/MEIS1 axis are developed for oxaliplatin resistant CRC patients, and our results suggest that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance in vivo and in vitro. Here, DNMT3A is linked to neoplasm.