The objective of this study was to assess whether Spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) gene expression could serve as a valuable prognostic and diagnostic biomarker in common cancers, drawing from insights in recent literature. We sought to verify this concept by utilizing data sourced from The Cancer Genome Atlas (TCGA) alongside clinical samples. In this bioinformatics and experimental study, SPOCD1 RNA-seq data from 12 common cancers were collected from TCGA Pan-Cancer Atlas using the R package "TCGA BIOLINKS" and normalized for analysis. Various analytical tools, including receiver operating characteristic (ROC) curves, Kaplan-Meier and Coxregression analyses, and pathway enrichment analysis via the molecular signatures database (MSigDB), were applied. Drug resistance/sensitivity correlations with SPOCD1 expression were explored using the Gene Expression Omnibus (GEO) database. Clinical colorectal cancer (CRC) samples, including both colon and rectal malignant samples, were also evaluated. The results showed elevated SPOCD1 expression in most cancers (9/12), with notable prognostic value in COAD, HNSC, KICH, and LIHC, and a correlation with poor prognosis in COAD for disease-free survival. ROC curve analysis suggested SPOCD1 as a diagnostic biomarker in the majority of cases (7/12), although this pattern was inconsistent in clinical CRC samples. Pathway enrichment analysis revealed a strong correlation between SPOCD1 expression and critical molecular pathways. Unlike former results, we found that SPOCD1 upregulated when interacting with PD-0325901. However, treating with Panobinostat led to downregulation. Both are as anticancer reagents. This study confirms the potential of SPOCD1 as a diagnostic and prognostic biomarker in prevalent cancers. However, extensive clinical data, particularly for CRC, are required to validate its reliability. Different COAD subtypes may exhibit varying correlations with SPOCD1 expression levels, underscoring the need for further investigation to fully understand its diagnostic and prognostic value.