Background: Colorectal cancer(CRC) is the fourth most prevalent cancer and the leading cause of cancer mortality worldwide. Drug resistance remains the main obstacle to the success of cytotoxic therapies. It is reported that soluble factors released by carcinoma-associated fibroblasts(CAFs) can induce the translocation of AKT, Survivin, P38 to the nucleus of tumor cells, which might be the mechanism of microenvironment-mediated drug resistance to nonspecific conventional chemotherapeutic agents, such as platinum compounds or 5-FU. Methods: Clinicopathological data of colorectal cancer patients who underwent chemotherapy (XELOX or FOLFOX) were collected, followed up and evaluated. p-AKT and survivin expression were assessed by immunohistochemical (IHC) staining. The relationships between p-AKT and survivin expression and patients’ resistance to chemotherapy were analyzed by Chi square respectively. The expression between p-AKT and survivin expression and progression-free survival(PFS) of patients were analyzed by Kaplan-Meier. Results: 51 CRC patients were enrolled in our research. Among them, 21 patients were resistant to chemotherapy(PD), and 30 patients were sensitive to chemotherapy(PR). P-AKT and survivin were assessed by IHC in 47 patients. Among them, 17 patients were p-AKT positive, and 29 patients were survivin positive. Patients of progressive disease(resistant to chemotherapy) were significantly associated with p-AKT positive and survivin positive(p = 0.009, 0.000). Poorer progression-free survival(PFS) was observed in patients with survivin positive compared to those with survivin negative(6.323±0.9m, 13.857±2.664m, Breslow chi square = 4.885, p value = 0.027). There is no significant difference between p-AKT expression and PFS(Breslow chi square = 2.403, p value = 0.121). Conclusions: CRC patients with p-AKT positive or survivin positive were more likely to be resistant to chemotherapeutic agents. CRC patients with survivin positive had a shorter DFS.