Previous work has demonstrated that precipitated (NM-200) and pyrogenic (NM-203) Amorphous Silica Nanoparticles (ASNPs) elicit the inflammatory activation of murine macrophages, with more pronounced effects observed with NM-203. Here, we compare the effects of low doses of NM-200 and NM-203 on human macrophage-like THP-1 cells, assessing how the pre-exposure to these nanomaterials affects the cell response to lipopolysaccharide (LPS). Cell viability was affected by NM-203, but not by NM-200, and only in the presence of LPS. While NM-203 stimulated mTORC1, neither ASNPs activated NFκB or the transcription of its target genes PTGS2 and IL1B. NM-200 and NM-203 caused a block of the autophagic flux and inhibited the LPS-dependent increase of Glutamine Synthetase (GS) expression. Both ASNPs suppressed the activation of caspase-1, delaying the LPS-dependent secretion of IL-1β. Thus, ASNPs modulate several important pathways in human macrophages, altering their response to LPS. NM-203 had larger effects on autophagy, mTORC1 activity and GS expression than NM-200, confirming the higher biological activity of pyrogenic ASNPs when compared with precipitated ASNPs.