Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, and their anomalous expression exert an essential role in the progression of many kinds of cancers, including colorectal carcinoma (CRC). The objective of this study was to investigate the role of lncRNA kcna3 and its underlying mechanism in CRC progression. The expression of lncRNA kcna3 in human CRC tissues and the adjacent non-tumor tissues was evaluated by RT-PCR. The correlations between lncRNA kcna3 expression levels and the overall survival (OS), as well as the clinicopathological features of CRC patients were analyzed. Gain-of-function and loss-of-function experiments were used to evaluate the effects of lncRNA kcna3 on the proliferation, apoptosis, migration, invasion and tumorigenesis of colon cancer SW620 cells. We found that lncRNA kcna3 was lowly expressed in CRC tissues, and its low expression was closely associated with patients’ higher TNM grade and the higher occurrence rate of lymphatic metastasis and distant metastasis, as well as shorter OS. Enhanced expression of lncRNA kcna3 inhibited SW620 cells’ proliferation, migration and invasion, and induced cell apoptosis in vitro, and repressed CRC tumor growth in vivo. Whereas knockdown of lncRNA kcna3 showed the opposite results. Mechanistically, up-regulation of lncRNA kcna3 decreased YAP1 protein expression and accelerated its degradation. The effects of lncRNA kcna3 overexpression on cell growth and tumorigenesis inhibition and apoptosis promotion were weakened when the expression of YAP1 was up-regulated. In conclusion, this study revealed that lncRNA kcna3 exerts a tumor-inhibit role in CRC progression through down-regulating YAP1 expression, indicating that lncRNA kcna3/YAP1 might be served as a new prognostic biomarker and therapeutic target for CRC.