Surgical resection and adjuvant therapy, which mainly involves 5-fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (LOHP) chemotherapy and recently targeted therapy, are the most common treatments of colorectal cancer (CRC). As to improve the therapeutic efficacy and assist with therapeutic decisions, there is an urgent need for prognostic and predictive molecular biomarkers. Recent evidence demonstrates that aberrations in alternative splicing process of cancer will provide candidate biomarkers for cancers to meet this need. In this review, we outline the fundamental mechanism of alternative splicing that plays a major role in protein diversity, and summarize the relationship between imbalance alternative splicing with cancer. Moreover, several alternative spliced variants and cancerspecific splicing events at the mRNA level in CRC, which may serve as diagnostic, predictive, prognostic markers of CRC, are also discussed. These specific splice variants or the RNA splicing machinery will be new, potential targets for the treatment of CRC that offers a specific site of anti-cancer chemotherapy.