Using friction force microscopy (FFM) under controlled environments, we have systematically investigated the humidity effect on the frictional properties of two important classes of self-assembled monolayers (SAMs), i.e., N-octadecyltrimethoxysilane (OTE,CH3(CH2)17Si(OCH3)3) on SiO2 (OTE/SiO2); and N-alkanethiols on Au (111), together with their respective substrates. Experimental results show that both OTE and alkylthiol SAMs can decrease the friction force between a Si3N4 atomic force microscope (AFM) tip and substrates. The nearly humidity-independent friction of the two kinds of SAMs indicates that these SAMs are ideal lubricants in applications of micro-electro-mechanical systems (MEMS) under different environments. The humidity dependence-as the humidity increases, the friction first increases and then decreases-of the two substrates, SiO2 and Au (111), can be explained by the adsorption of water. The decrease in the friction at high humidity is attributed to the low viscosity in the multilayers of water, while the increase in the friction at low humidity can be explained by the high viscosity between the water monolayer and the surfaces (AFM tip and sample), possibly due to the confinement effects. The effect of modification of the AFM tip with alkanethiol molecules on the humidity dependence of Au (111) friction has also been investigated.