Objective To investigate the potential value of miR-200a-3p and its downstream target gene programmed cell death 4 （PDCD4） in the diagnosis and prognosis of colorectal cancer（CRC）. Methods A cohort containing 120 pairs of CRC tissue samples and corresponding adjacent tissue samples were collected from CRC patients who underwent radical resection or palliative resection from January 2017 to September 2019. Another cohort included 50 patients diagnosed with CRC，and preoperative and postoperative serum samples were collected from these patients before and after surgery from January 2019 to January 2020. RT-qPCR was used to measure the expression of miR-200a-3p in CRC tissue and cell lines. CRC cells were transfected with plasmids targeting miR-200a-3p（si-miR-200a-3p） and siRNAs negative control（si-NC） and plasmids with miR-200a-3p overexpression（miR-200a-3p-OE） and PDCD4 overexpression（PDCD4），and Cell Counting Kit-8 assay，colony formation assay，and Transwell assay were used to observe the influence of miR-200a-3p on the growth of CRC cells. Female BALB/c nude mice were randomly divided into Vector group，miR-200a-3p overexpression group（miR-200a-3p-OE group），and miR-200a-3p overexpression+PDCD4 overexpression group（miR-200a-3p-OE+PDCD4 group）. A mouse model of distant metastasis was established，and the fluorescence intensity of lung metastasis was monitored，as well as the number of lung metastasis nodules. Results The expression of miR-200a-3p was upregulated in CRC tissue and cell lines. The high expression of miR-200a-3p was significantly associated with tumor size，tumor metastasis，and TNM stage. The expression of miR-200a-3p could be regarded as an independent prognostic biomarker for overall survival（hazard ratio ［HR］=2.077，95%CI=1.079-3.998，P=0.029） and disease-free survival（HR=2.927，95%CI=1.179-7.270，P=0.021）. Functional study revealed that miR-200a-3p could bind to the 3’-UTR region of PDCD4 and reduced the expression of PDCD4 in CRC cells. Overexpression of PDCD4 inhibited the promoting effect of miR-200a-3p on the proliferation，colony formation，migration，and invasion of CRC cells. In the mouse model of metastasis and caudal vein injection，the miR-200a-3p-OE+PDCD4 group had significant reductions in lung colonization and lung metastatic lesions compared with the miR-200a-3p-OE group（P<0.05），which was consistent with the in vitro results. Conclusion There is a significant increase in the expression of miR-200a-3p in CRC cells，tissue，and serum，and it can be used as a biomarker for diagnosis and prognosis. Overexpression of miR-200a-3p promotes the progression of CRC by inhibiting PDCD4 expression.