Context. The Southern Photometric Local Universe Survey (S-PLUS) is a project to map ~9300 sq deg of the sky using twelve bands (seven narrow and five broadbands). Observations are performed with the T80-South telescope, a robotic telescope located at the Cerro Tololo Observatory in Chile. The survey footprint consists of several large contiguous areas, including fields at high and low galactic latitudes, and towards the Magellanic Clouds. S-PLUS uses fixed exposure times to reach point source depths of about 21 mag in the griz and 20 mag in the u and the narrow filters. Aims. This paper describes the S-PLUS Data Release 4 (DR4), which includes calibrated images and derived catalogues for over 3000 sq deg, covering the aforementioned area. The catalogues provide multi-band photometry performed with the tools DoPHOT and SExtractor – point spread function (PSF) and aperture photometry, respectively. In addition to the characterization, we also present the scientific potential of the data. Methods. We use statistical tools to present and compare the photometry obtained through different methods. Overall we find good agreement between the different methods, with a slight systematic offset of 0.05 mag between our PSF and aperture photometry. We show that the astrometry accuracy is equivalent to that obtained in previous S-PLUS data releases, even in very crowded fields where photometric extraction is challenging. The depths of main survey (MS) photometry for a minimum signal-to-noise ratio S/N = 3 reach from ~19.5 for the bluer bands to ~21.5 mag on the red. The range of magnitudes over which accurate PSF photometry is obtained is shallower, reaching ~19 to ~20.5 mag depending on the filter. Based on these photometric data, we provide star-galaxy-quasar classification and photometric redshift for millions of objects. Results. We demonstrate the versatility of the data by presenting the results of a project to identify members of four Abell galaxy clusters in the Local Universe. The S-PLUS DR4 data allow for a reliable assessment of cluster membership out to a large radius corresponding to 5 × r200. The S-PLUS DR4 can be accessed through the survey data portal. All the software used to generate the catalogues for this release and the scientific investigation presented is available in the collaboration GitHub repository. Conclusions. The S-PLUS DR4 consists of a large, calibrated public dataset, providing powerful ways for studying Galactic and extra-galactic objects through an extensive set of (broad and narrow) filters.