hArpNβ, an actin-related protein located within the nucleus, is a subunit of the human SWI/SNF chromatin remodeling complex. hArpNβ has been proposed to regulate the assembly and activity of the hSWI/SNF complex. Sequence comparisons of the potential ArpN homologs with β-actin showed that the ArpNs have the divergent subdomains Ib and IIb in addition to the unique N-terminal short insert, MS(G/A)—(V/L)YGG. Since the proposed function of hArpNβ requires more than two distinct but concurrently operating surfaces, we examined whether the disruption of one operating surface of hArpNβ results in dominant-negative phenotype. When overexpressed in HeLa or 293T cells, the subdomain Ib or IIb hybrids, in which the subdomain Ib or IIb of hArpNβ was replaced with that of β-actin, respectively, showed no effect on cell survival. On the other hand, the overexpression of the N-terminal deletion mutant of hArpNβ resulted in cell death probably through apoptotic process. These results indicate that the proper function of hArpNβ is essential for cell survival in human cells. Furthermore, they suggests the possibility that the N-terminal short sequence is indispensable for the chromatin remodeling activity or the assembly of the hSWI/SNF complex after the binding of hArpNβ with functionally essential partner proteins.