This study evaluated CD44 and COX-2 expression in colorectal cancer (CRC) and analyzed its relationship with the clinicopathological characteristics. The prognostic impact on patient survival was compared between the two proteins. CD44 and COX-2 mRNA levels in 42 primary CRCs were analyzed using quantitative real-time PCR, with normalization relative to GAPDH. The cycle threshold (Ct) values were measured, and results are expressed as the Ct ratios of CD44 or COX-2 to GAPDH. The COX-2 Ct ratio was much lower in cases of lymphovascular invasion by the tumor than for no invasion (P = 0.004). During follow-up for a median of 40 months, there was no significant difference in the median CD44 Ct ratio between survivors and non-survivors (P = 0.362), whereas the COX-2 Ct ratio was significantly associated with survival at the time of data analysis (P = 0.042). The survival of colorectal cancer patients with a high COX-2 Ct ratio was significantly longer than that of patients with a low COX-2 Ct ratio (P = 0.048). This study suggests that COX-2 expression has a more significant impact than CD44 expression on the survival of CRC patients. Further studies are needed to resolve these issues with a large sample size.