Abnormal brain lateralization has been implicated in schizophrenia but few studies have focused on the variability of resting-state fMRI signal and its lateralization in schizophrenia. Here we utilized standard deviations (SD) to quantify the variability of resting-state fMRI signal and measured the lateralization index (LI), on the basis of SD of the resting-state fMRI signal in order to assess the difference of brain signal variability across the hemispheres. We recruited 180 patients with schizophrenia and 358 age- and sex-matched healthy volunteers. Between-group comparison revealed that in comparison to healthy volunteers, schizophrenia patients have significantly higher SD of resting-state fMRI activity in left inferior temporal, left fusiform, and right superior medial frontal cortex, and lower SD in right precuneus, posterior cingulum on both sides, right lingual, and left calcarine in the occipital region. Using region of interest approach, most brain regions showed increased leftward lateralization in patients with schizophrenia, as compared with healthy controls. SD and LI were also found to be correlated to age of onset or duration of illness. These results provide further evidence that abnormal variability and lateralization exist in schizophrenia patients, and abnormality in fusiform, lingual and inferior temporal could have potential help to identify the dysfunctional brain lateralization in schizophrenia.