Aim: The potential functions and underlying mechanism of microfibrillar-associated proteins (MFAPs) are explored in human cancers. Materials & methods: Here, we examined the expression profiles, prognostic values, epigenetic and genetic alterations of MFAPs in human cancers from public omics repository. Results: Among MFAPs family, MFAP4 was frequently downregulated in the most human cancers and high mRNA expression of MFAP4 significantly correlated with better overall survival in breast cancer. DNA hypermethylation in the promoter of MFAP4 decreased its mRNA expression. MFAP4 strongly associated with pathway in impairment and alteration of the elastic fibers. Conclusion: This integrated analysis provides new insights into MFAPs in human cancers and indicates that MFAP4 could be used as novel biomarker for developing therapies against human cancers.