Asbestos (Mg‐hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter‐length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg‐ and two NiNTs of different lengths were assessed for cytotoxicity and pro‐inflammatory responses in THP‐1 macrophages and human bronchial epithelial lung cells (HBEC3‐KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET‐ and BJH analysis, and chemical composition by XRD. The different Mg‐ and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro‐inflammatory cytokines in THP‐1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3‐KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF‐β responses than chrysotile in both cell models. In conclusion, the pro‐inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP‐1 macrophages, but not in HBEC3‐KT cells. Notably, the shortest NTs showed no or little pro‐inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.