In the process of a series of geological core drilling projects in the hilly areas of southern China， a number of technical difficulties have been encountered， including the karst cave crossing in the karst cavity area， the safe drilling in the lost return layer at the bottom of the well， the coring problem in the loose mudstone， sandstone and gravel layer， drilling difficulty in the water-sensitive formation， the stable drilling in the strong deflecting area， and the relocation difficulty in the deep cutting area. Therefore， the following technical measures were taken in response to the above difficulties： （1）the “double casing+half filling”method is taken to cross the karst caves， （2） the comprehensive technical measures of “top leakage+plugging+lubricating drilling tool”； （3） the advanced coring with casing while drilling and multi-layer casing wall protection technology， and the special sampling drilling tool with aperture convergence and the telescopic leakage joint are innovatively applied， which significantly improves the core recovery rate， （4） a low solid-phase anti-sloughing flushing fluid and strengthening solid-phase control， reducing the rotation speed and back footage， as well as rapid casing support response to ensure the hole safety； （5） the calculation method based on the mechanical model of continuous beam wire-line coring drilling tool， and the measures of low pressure lifting， drilling rig foundation reinforcement and concentricity improvement are adopted to achieve the purpose of anti-deviation and straightening； （6） the efficient scheme using drones for relocation. The results of this paper provide an important reference for drilling construction under similar environment and complex geological conditions.