Several studies have demonstrated that calpain‑1 is involved in a variety of pathophysiological processes, including tumorigenesis. However, the clinical relevance and role of calpain‑1 in colorectal cancer (CRC) are unclear. Filamin A (FLNA) is an actin‑binding protein that participates in cancer progression and can be cleaved by calpain‑1. In the present study, the protein expression levels of calpain‑1 and FLNA were detected by immunohistochemistry in 467 matched cancerous and paracancerous tissues from patients with CRC. The staining results and the clinicopathological characteristics of the patients were comprehensively analyzed. A high expression level of calpain‑1 was strongly associated with age, metastasis, Dukes stage and survival time but not with sex, histologic grade, tumour location or tumor size. By contrast, a low expression level of FLNA was significantly associated with tumor size, histological grade, metastasis, Dukes stage and survival time, but not with age, sex, or tumor location. Kaplan‑Meier survival analysis demonstrated that patients with calpain‑1 overexpression had a shorter mean overall survival (OS) than patients with lower levels of calpain‑1 expression. Unlike high levels of calpain‑1, high levels of FLNA were associated with longer OS than lower levels of FLNA expression. Furthermore, calpain‑1 expression was inversely correlated with FLNA expression. The relationship between calpain‑1 and FLNA was further confirmed using CRC cell lines in vitro. When calpain‑1 expression decreased in CRC cells, FLNA expression increased. Furthermore, calpain‑1 knockdown in CRC cells resulted in decreased proliferation, colony formation, migration and invasion. The present findings suggest that calpain‑1 overexpression predicted a poor outcome in patients with CRC and promoted tumor progression, possibly via FLNA downregulation.